[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

CN1055930C - Steroalkenol polyfluohydrocarbyl sulfonate compound and its deriv., use and preparing process - Google Patents

Steroalkenol polyfluohydrocarbyl sulfonate compound and its deriv., use and preparing process Download PDF

Info

Publication number
CN1055930C
CN1055930C CN94113929A CN94113929A CN1055930C CN 1055930 C CN1055930 C CN 1055930C CN 94113929 A CN94113929 A CN 94113929A CN 94113929 A CN94113929 A CN 94113929A CN 1055930 C CN1055930 C CN 1055930C
Authority
CN
China
Prior art keywords
compound
steroidal
enol
ketone
oxo
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN94113929A
Other languages
Chinese (zh)
Other versions
CN1107478A (en
Inventor
田伟生
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Institute of Organic Chemistry of CAS
Original Assignee
Shanghai Institute of Organic Chemistry of CAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shanghai Institute of Organic Chemistry of CAS filed Critical Shanghai Institute of Organic Chemistry of CAS
Priority to CN94113929A priority Critical patent/CN1055930C/en
Publication of CN1107478A publication Critical patent/CN1107478A/en
Application granted granted Critical
Publication of CN1055930C publication Critical patent/CN1055930C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Landscapes

  • Steroid Compounds (AREA)

Abstract

The present invention relates to a steroid enol polyfluohydrocarbyl sulfonate compound, derivatives thereof, the application and a preparation method thereof. The compound similar to enol trifluoromethyl sulfonate can react with various nucleophilic reagents; the compound is an important intermediate of steroid medicines; the compound can be produced in the reaction between a steroid-3-ketone compound and polyfluoro-sulfuryl fluorine in the presence of a compound containing nitrogen atoms which have lone-pair electrons. The yield is high; polyfluoro-sulfuryl fluorine used is cheap, convenient and easy to obtain; the reagent has stable property; the reaction has convenient operation and good chemical selectivity.

Description

A kind of steroidal enol polyfluoro alkyl sulfonate compound and derivative thereof, Use and preparation method
The present invention relates to a kind of steroidal enol Polyfluoroalkyl sulfonate compound and derivative thereof, Use and preparation method.This steroidal enol Polyfluoroalkyl sulfonate compound and derivative thereof can be obtained by polyfluoro sulfonic acid halide and carbonyl compound reaction; this method is particularly useful for the synthetic of steroidal compounds that 3-perfluoroalkyl or alkoxyl group alkylsulfonyl replace, and product is the important intermediate of steroid drugs.
Enol trifluoromethane sulfonic acid ester can react with thiazolinyl positive ion form and various nucleophilic reagent, and is applied to having various substituent alkene synthetic (P.J.stang etc., Synthesis, 1982,85; W.J.Scott etc., Acc.Chem.Res, 1988,21,47.), as be applied to synthetic (D.A.Holt etc., J.Med.Chem, 1990,33,943) of steroidal 5 inhibitors 3-carboxyl steroid compound.Though in chemical laboratory, enol trifluoromethane sulfonic acid ester can make by carbonyl compound and trifluoromethyl sulfonic acid anhydride reaction easily,, three fluorosulfonic anhydride not only cost an arm and a leg, and the character instability, and reaction preference is low, therefore limits its practical application on industrial production.For example, when steroidal compounds 1 changes into corresponding enol trifluoromethane sulfonic acid ester 2, because trifluoromethyl sulfonic acid anhydride lacks reaction preference preferably, give the enol trifluoromethane sulfonic acid ester of phase except that generating in the reaction, also be accompanied by the generation of unwanted by product 3 simultaneously:
Figure C9411392900041
The yield that this has not only reduced reaction product 2 has also increased and has separated the difficulty that obtains product 2 pure sample product, has finally not only increased the cost of enol trifluoromethane sulfonic acid ester, and has limited their application.For making the enol sulphonate can on industrial production, obtain with the reaction of various nucleophilic reagents to use; seek low-cost steroidal enol Polyfluoroalkyl sulphonate and derivative thereof, stable in properties, inexpensive, enol sulfonylation agent and be very important with the method that enol sulfonylation agent selectivity prepares steroidal enol Polyfluoroalkyl sulphonate and derivative thereof with higher reaction preference.
The purpose of this invention is to provide a kind of low price, enol Polyfluoroalkyl sulphonate and derivative thereof that purity is high.
Another object of the present invention provides a kind of method than synthetic enol Polyfluoroalkyl sulphonate of highly selective and derivative thereof, and this method is particularly useful for the synthetic of 3 steroidal compounds that replace perfluoroalkyl sulfonate esters and derivative thereof.
The purposes that also has a purpose to provide this class steroidal enol Polyfluoroalkyl sulphonate and derivative thereof of the present invention.
A kind of enol Polyfluoroalkyl sulphonate provided by the invention and derivative thereof are to have following molecular formula:
Figure C9411392900051
Wherein Or , R 1=H or CH 3, R 2=H, CH 3Or C 2H 5, R 3=CONR ' R ",
Figure C9411392900054
C 1-10Alkyl, CO 2CH 3, CN or OH, R ', R "=H, CH 3, C 2H 5, (CH 3) 2CH, (CH 3) 3C ,-(CH 2)-,-(CH 2) 3-,-(CH 2) 4-,-(CH 2) 5-,
Figure C9411392900055
Or
Figure C9411392900056
, R 4=H, C 2H 5, CH 3C ≡ C-, HC ≡ C-, CF 3, R 5Or R 6=H, F, Cl, OH, CH 3, CF 3, CH 2=or O,
Figure C9411392900061
Y=X (CF 2CF 2O) n, CF 3(CF 2) m, X=F, Cl, Br, I, H, n=0,1 or 2, m=0-5.The N-tertiary butyl-3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-androstane-3; 5-diene-17 β methane amide; 3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-5 α-androstane-3-alkene-17-ketone; 3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-5 α-steroid-3-alkene 16 β; the 20-glycol acetone that contracts; 17 Alpha-Methyls-3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-androstane-3; 5-alkene-17 β-alcohol; 3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-6-oxo-5 α-courage steroid-3-alkene-24 carboxylate methyl ester; 3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-pregnant steroid-3; 5-diene-ketone-20; N-tertiary butyl 3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-androstane-3; 5-diene-17 β-methane amide; the N-tertiary butyl-3-[(PFO) sulfonyloxy]-androstane-3; 5-diene-17 β-methane amide; the N-tertiary butyl-3-(methoxy acyl group)-androstane-3; 5-diene-17 β-methane amide; 3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-androstane-3; 5-diene-17-ketone; the 3-[(perfluorinated butane) sulfonyloxy]-pregnant steroid-3; 5-diene-20-ketone; 17 alpha-acetylenes base-18-methyl-19-nor base-3-3 (5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy-androstane-3; 5-diene-17 β-alcohol; 3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-16-methyl-5 α-pregnant steroid-3; 16-diene-20-ketone; the N-tertiary butyl-3-[(8-hydrogen-3; 6-dioxo PFO sulfonyloxy]-androstane-3,5-diene-17 β-methane amide etc.
5-iodo-3-oxo octafluoro pentane sulfonic acid fluoride is the synthetic intermediate of fluorochemical surfactant Polyfluoroalkyl sulfonate, can obtain (Shanghai Organic Chemistry Institute, Chinese Academy of Sciences's perfluorinated sulfonic acid group, chemical journal, 1979,37,317 easily; Scientia Sinica, 1978,21,773), can all can react with alkyl alcohol and the aminated compounds thereof that phenol, polyfluoro replace (Chen Qingyun, chemical journal, 1982,40,33 of it and analogue thereof; HuangWeiyuan etc., Acta Chim.Sinica, 1983,1,58; The Chen Li Buddhist, chemical journal, 1983,9,860).We find that 5-iodo-3-oxo octafluoro sulphur pentane acyl fluorides and relevant sulfonic acid fluoride thereof can transform carbonyl compound easily and become corresponding enol Polyfluoroalkyl or alkyl or alkoxyl group sulphonate.The enol sulfonylation agent that adopts among the present invention can have following molecular formula: YCF 2CF 2SO 3F, wherein Y=X (CF 2CF 2O) n or CF 3(CF 2) m, X=F, Cl, Br, I or H, n=0,1 or 2, m=0-5.
The method for preparing steroidal enol Polyfluoroalkyl sulphonate of the present invention can be from steroidal 3-ketone compound by making enol polyfluoro sulphonate and derivative thereof with above-mentioned sulfonic acid fluoride reaction easily.
Method of the present invention can be from molecular formula
Figure C9411392900071
Steroidal-3-ketone compound be starting raw material, wherein
Figure C9411392900072
Or
Figure C9411392900073
R 1=H or CH 3, R 2=H, CH 3Or C 2H 5, R 3=CONR ' R ",
Figure C9411392900074
C 1-10Alkyl, CO 2CH 3Or OH etc., R ', R "=H, CH 3, C 2H 5, (CH 3) 2CH, (CH 3) 3C ,-(CH 2) 2-,-(CH 2) 3-,-(CH 2) 4-,-(CH 2) 5-, Or
Figure C9411392900076
, R 4=H, C 2H 5, CH 3C ≡ C-, HC ≡ C-, CF 3,-CN etc., R 5Or R 6=H, F, Cl, OH, CH 3, CF 2Cl, CF 3, CH 2=or O, , adopt sulfonylation agent YCF 2CF 2SO 3F, wherein Y=X (CF 2CF 2O) n, CF 3(CF 2) m, X=F, Cl, Br, I, H, n=0,1 or 2, m=0-5.In the presence of the nitrogenous compound that has lone pair electron on the nitrogen-atoms, make steroidal enol polyfluoro sulfonic acid fluoride compound and derivative thereof with above-mentioned enol sulfonated reagent reaction.The nitrogenous compound of band lone pair electron and the mole ratio of enol sulfonylation agent are 1 on steroidal-3-ketone compound, the nitrogen-atoms: 1-20: 1-20.The nitrogenous compound, the sulfonylation agent that have lone pair electron on the more nitrogen-atoms are favourable to reaction.From considering that economically three's mol ratio is with 1: 2-8: 2-8 is good.
The nitrogenous compound that has lone pair electron on the nitrogen-atoms that is adopted in the method for the present invention can be diethylamine, triethylamine, diisopropylethylamine, trimethylpyridine, lutidine, 1,5-diaza-bicyclo [4,3,0] nonene-5 (DBN), 1,8-diaza-bicyclo [5,4,0] hendecene-7 (DBU), 1-butyl imidazole etc.
Method of the present invention is preferably in the solvent carries out, and described solvent is polar solvent or aromatic hydrocarbons preferably, as benzene, methylene dichloride, trichloromethane, acetonitrile, toluene, dimethylbenzene, dimethyl formamide, dioxane and glycol dimethyl ether etc.
Method of the present invention, usually temperature of reaction is a room temperature to 160 ℃, the further raising of temperature of reaction also can make reaction carry out.Reaction times is 0.5-20 hour, usually at 2-8 hour.
Product steroidal enol polyfluoro sulphonate of the present invention and derivative thereof, its reactivity worth is analogous to enol trifluoromethane sulfonic acid ester, and it can synthesize required molecules of interest with various nucleophilic reagent reactions.Steroidal enol Polyfluoroalkyl sulfonate compound of the present invention and derivative thereof, on the 3-bit substituent, can adopt method commonly used to change into the steroidal compounds of 3 carboxylic acid ester groups, carboxyl, cyano group, hydrogen base or amide group etc. easily, especially can be used as the important intermediate of steroid drugs.As the N-tertiary butyl-3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-androstane-3,5-diene-17 β methane amide, under pd (0) catalysis, react in methanol solution with carbon monoxide and to obtain corresponding 3-carboxylate steroid compound, be hydrolyzed into steroidal 5 inhibitor through ester again.
Method of the present invention is the yield height not only, usually at 40-90%, and compare as the method for enol sulfonated reagent with trifluoromethyl sulfonic acid anhydride, have also that polyfluoro sulfonic acid fluoride reagent conveniently is easy to get, low price, reagent stable in properties, operation is convenient, has advantages such as good chemo-selective.
Can further understand content of the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1, the N-tertiary butyl-3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-androstane-3,5-diene-17 β methane amide (4) synthetic
Dissolving 742mg17 β-tertiary butyl formyl radical-androstane-4-alkene-3-ketone under heated and stirred (temperature 80-90 ℃), slowly drips DBU and 5-hydrogen-3-oxo-octafluoro pentane sulfonic acid fluoride in 5ml toluene.React after 6 hours, cooling is reacted to room temperature, filters by a short silicagel column, collects filtrate and elutriant.Decompression desolventizes and obtains product.Yield 77%.
Compound analysis result: m.p.78.5-80.7 ℃ 1HNMR (DCCl 3, 300MH 2): 0.73 (3H, S, 18-H 2), 0.97 (3H, S, 19-H 3),
1.36(9H，S，N +)，5.09(1H，brs，NH)，
5.57(1H，m，6-H)，
5.86(1H，tt，J＝3，52.4H 2，HCF 2)， 6.0(1H，S，4-H)ppm 19FNMR(DCCl 3)：3.5(S，2F，-OCF 2-)，10.4(S，2F，-CF 2O-)，
35.9(S，2F，-CF 2SO 2-)，
60.0(d，2F，J＝53.0H 2，HCF 2-)ppmMS?m/e：651(M +)，370，314，57，
Embodiment 2,3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-5 α-androstane-3-alkene-17-ketone (5)
With 1mmol androstane-3, the 17-diketone is dissolved in the 6ml benzene, Dropwise 5 mmol triethylamine and 5-hydrogen-3-oxo-octafluoro penta sulfonic acid fluoride under constantly stirring in the time of 60-80 ℃, react after 3 hours, be cooled to room temperature, filter by silicagel column, filtrate is obtained product after desolventizing, productive rate 91%.
Compound analysis result: m.p.50.0-51.0 ℃ of IR υ (KCl): 1760,1704,1200cm -1 1HNMR (DCCl 3, 300MH 2): 0.83,0.88,5.67,5.87ppm 19FNMR (TFA is 0, High-Field for just): 60.0,36.0,3.5,10.3ppmC 23H 28O 5SF 8Calculated value C48.59 H4.93 measured value C48.52 H4.96
Embodiment 3,3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-5 α-pregnant steroid-3-alkene-16 β, the 20-glycol acetone (6) that contracts
With 2mmol3-oxo pregnant steroid-16, the 20-glycol contracts acetone solution in the 10ml ethylene dichloride, drip 10mmol lutidine and 5-hydrogen-3-oxo-octafluoro at reflux temperature with under stirring for sulfonic acid fluoride, react after 5 hours, cooling, filter by silicagel column, filtrate is obtained product after desolventizing, productive rate 76%.
Compound analysis result: m.p.92.4-93.4 ℃ of IR υ (KCl): 1680,1100-1220cm -1 1HNMR (DCCl 3, 300MH 2): 0.82,0.89,1.19,1.33,3.85,4.15,5.65,
5.86ppm 19FNMR (CDCl 3): 3.5,10.1,36,59.5ppmMS m/e:639 (M +-CH 3), 579 (M +-CH 3-HOAC), and 315,297,246C 28H 38O 6SF 8Calculated value C51.38 H5.81 F23.24 S4.89 measured value C51.45 H5.69 F23.61 S5.17
Embodiment 4,17 Alpha-Methyls-3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-androstane-3, the preparation of 5-diene-17 β-alcohol (7)
17 Alpha-Methyls-17 beta-hydroxy androstane-4-alkene-3-ketone raw material is obtained the oily matter product by embodiment 1 method after synthetic.Productive rate 44%.
Compound analysis result: IR υ (KCl): 3500 (OH), 1680 (C=C) cm -1 1HNMR (CDCl 3, 300MH 2): 0.9 (3H), 0.99 (3H), 1.23 (3H), 5.57 (1H),
5.87(1H)，5.67(1H)ppmMS?m/e：564(M +-H 2O)，549(M +-H 2O-CH 3)，
283(M +-H 2O-HCF 2CF 2OCF 2CF 2SO 3)
Embodiment 5,3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-6-oxo-5 α-courage steroid-3-alkene-24 carboxylate methyl ester (8) synthetic
With 1mmol 3,6-dioxo but sour methyl esters are dissolved in the 10ml acetonitrile solvent, under 60 ℃ of stirrings, with 10mmol diethylamine and 5-hydrogen-3-oxo-octafluoro for sulfuryl bromide reaction 10 hours, handle the samely, obtain product, productive rate 32%.
Compound analysis result: m.p.89.6-91.3 ℃ IR:1730 (C=O), 1700 (C=O) cm -1 1HNMR (CDCl 3, 300MH 2): 0.68 (3H), 0.78 (3H), 0.93 (3H), 3.67 (3H)
5.67 (1H), 5.87 (1H) ppm 19FNMR (CDCl 3): 3.5 (S, 2F), 10.3 (S, 2F), 36 (S, 2F), 60.0 (d, 2F) ppmMS m/e:667 (M +-15), 633,609,525,401C 29H 38O 7SF 8Calculated value C51.0 H5.57 measured value C51.07 H5.59
Embodiment 6,3[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-pregnant steroid-3, the preparation of 5-dienone-20 (9)
With pregnant steroid-4-alkene-3,20-diketone raw material is pressed the preparation of embodiment 2 methods, yield 77%.
Compound analysis result: m.p.72.7-73.9 ℃ of IR υ (KCl): 1760 (C=O) cm -1 1HNMR (CDCl 3, 300MH 2): 0.67 (S, 3H), 0.97 (S, 3H), 2.13 (S, 3H),
5.58(m，1H)，6.00(d，1H)，5.86(tt，1H)MS?m/e：594(M +)，313，295
Embodiment 7, the N-tertiary butyl-3-[(PFO) sulfonyloxy]-androstane-3, the preparation of 5-diene-17 β-methane amide (10)
Dissolving 1mmol17 β-tertiary butyl formyl radical-androstane-4-alkene-3-ketone under 80 ℃ of stirrings, drips 8mmolDBU and perfluoro octane sulfonyl fluoride in 6ml toluene, react after 8 hours, by preceding method handle the compound of 41% yield.
Compound analysis result: m.p.129.2-131.4 ℃ 1HNMR (CDCl 3, 300MH 2): 0.72 (3H, S), 0.97 (3H, S), 1.35 (9H, S),
5.07 (1H, S), 5.58 (1H, m), 6.01 (1H, d) ppmMS m/e:853 (M +), 370,57C 32H 36O 4SFN calculated value C45.02 H4.22 measured value C49.05 H4.15
Embodiment 8, N-tertiary butyl 3-(methoxy acyl group)-androstane-3, the preparation of 5-diene-17 β-methane amide (11)
Dissolving steroidal polyfluoro sulfonate compound (2) adds triethylamine and catalyzer-two (triphenylphosphine) palladium diacetate of equivalent in exsiccant methyl alcohol and dimethyl formamide, under-carbonoxide atmosphere, and 60-80 ℃ of stirring reaction 4 hours.It is assorted to remove by filter insoluble character, and filtrate concentrates, crude product through column chromatography handle product, yield 92%.
Compound analysis result: m.p.145.0-145.7 ℃ of IR υ max:3350 (NH), 1720 (C=O), 1260 (C-O), 1660 (C=O), 720cm -1 1HNMR:0.72 (3H, S), 0.91 (3H, S), 1.36 (9H, S), 3.75 (3H, S),
5.13(1H，S)，5.80(1H，m)，7.04(1H)ppmMS?m/e：413(M)，414(M +1)，398(413-CH 3)，366(M-C 3H 7)，381，310，
248，57
Embodiment 9,3-[(5-fluoro-3-oxo octafluoro pentane) sulfonyloxy]-androstane-3, the preparation of 5-diene-17-ketone (12)
With androstane-4-alkene-3, it is synthetic that 17-diketone raw material is pressed embodiment 1 method, obtains product.Productive rate 49%.
Compound analysis result: m.p.71.7-73.5 ℃ of IR υ (film): 1740 (C=O), 1640 (C=O) cm -1 1HNMR (DCCl 3, 300MH 2): 0.92 (3H, S), 0.995 (3H, S), 5.61 (1H, m),
6.02(1H，d)，5.88(tt)ppmMS?m/e：566(M +)，285，267，243，225，213，57
Embodiment 10,3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-preparation of courage steroid-3-alkene (13)
Steroid-3-ketone is the method for raw material and embodiment 1, obtains the oily matter product to adopt courage, productive rate 80%.
Compound analysis result: IR υ (film): 1680 (C=C), 1120-1190 (SO 3-) cm -1 1HNMR (DCCl 3, 300MH 2): 0.66 (3H, S), 0.79 (3H, S), 0.85 (3H, d),
0.87 (3H, d), 0.90 (3H, d) ppm 19FNMR:4.3 (2F, S), 11 (2F, S), 36.5 (2F, S), 60 (2F, S) ppmMS m/e:667 (M ++ 1), 511,497,443C 31H 46O 4F 8S calculated value C55.86 H6.91 measured value C56.30 H7.11
Embodiment 11, the 3-[(perfluorinated butane) sulfonyloxy]-pregnant steroid-3,5-diene-20-ketone (14) synthetic
With the pregnant steroid of 1mmol-4-alkene-3, the 20-diketone is dissolved in the 10ml glycol dinitrate ether solvents, under reflux temperature with 2mmol perfluorinated butane sulfonic acid iodide and DBU reaction after 5 hours, product behind column chromatography for separation and purifying, yield 60%.
Compound analysis result: IR υ (KCl): 1710 (C=O) cm -1 1HNMR (COCl 3, 300MH 2): 0.68 (3H, S), 0.97 (3H, S), 2.12 (3H, S),
5.56 (1H, m), 6.01 (1H, d) ppmMS m/e:596 (M +), 313,295,149,43, C 25H 29O 4SF 9Calculated value C50.34 H4.87 measured value C50.08 H4.77
Embodiment 12,17 alpha-acetylenes base-18-methyl-19-nor base-3-[(5-hydrogen-3-oxidation octafluoro pentane) sulfonyloxy]-androstane-3,5-diene-17 β-alcohol (15) synthetic
2mmol17 alpha-acetylenes base-17 β-alcohol-18-methyl-19-nor base-androstane-4-alkene-3-ketone is dissolved in the toluene, under reflux temperature, reacted 6 hours, obtain 45% productive rate with 5mmol5-hydrogen-3-oxo octafluoro pentane sulfonic acid fluoride and triethylamine.
Compound analysis result: IR υ (KCl): 3500 (OH), 2100 (C=C) cm -1 1HNMR (CDCl 3, 300MH 2) 5.54 (1H, m), 5.86 (1H, tt), 5.68 (1H, d) ppmMS m/e:576 (M +), 558 (M +-H 2O) C 25H 28O 4SF 8Calculated value C52.08 H4.86 measured value C53.05 H4.81
Embodiment 13,3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-16-methyl-5 α-pregnant steroid-3,16-diene-20-ketone (16) synthetic
2mmol16-methyl-pregnant steroid-3,20 diketone, 20mmol5-hydrogen-3-oxo octafluoro pentane sulfonic acid fluoride and DBU after 10 hours, through column chromatographic isolation and purification, are obtained the product of 78% productive rate 60 ℃ of reactions.
Compound analysis result: IR υ (KCl): 1690 (C=O), 1640 (C=C) cm -1 1HNMR (CDCl 3, 300MH 2): 0.78 (3H, S), 0.98 (3H, S), 2.13 (3H, S),
1.80 (3H, S), 5.54 (1H, m), 5.86 (1H, tt), ppmMS m/e:592 (M +), 313,295C 26H 32O 4SF 8Calculated value C52.70 H5.41 measured value C51.50 H5.35
Embodiment 14, the N-tertiary butyl-3-[(8-hydrogen-3,6-dioxo PFO) sulfonyloxy]-androstane-3,5-diene-17 β-methane amide (17) synthetic
With 1mmol17 β-tertiary butyl formyl radical-androstane-4-alkene-3-ketone, 15mmol8-hydrogen-3,6-dioxo perfluoro octane sulfonyl fluoride and acetonitrile reacted 20 hours down at 30-40 ℃, after separation and purification, obtained 40% product.
Compound analysis result: IR υ (KCl): 1690 (CONH +) cm -1 1HNMR (CDCl 3, 300MH 2): 0.74 (3H, S), 0.96 (3H, S), 1.35 (9H, S),
5.08(1H，brs)，5.58(1H，m)，5.88(12H，tt)，
6.0(1H，S)ppm
Embodiment 15, the N-tertiary butyl-3-[(5-hydrogen-3-oxidation octafluoro pentane) sulfonyloxy]-androstane-3,5-diene-17 β-methane amide (4) synthetic
Dissolve 17 β-tertiary butyl formyl radical-androstane-4-alkene-3-ketone in toluene, 80-90 ℃ and stir under, drip DBU and 5-iodo-3-oxidation octafluoro pentane sulfonic acid fluoride, react after 10 hours, decompression desolventizes, again through silica gel column chromatography separation, yield 28%.Compound is through IR, 1HNMR and m.p. analyze with embodiment 1.

Claims (10)

1. steroidal enol Polyfluoroalkyl sulfonate compound is characterized in that its molecular formula is:
Figure C9411392900021
Wherein
Figure C9411392900022
Or , R 1=H or CH 3, R 2=H, CH 3Or C 2H 5, R 3=CONR ' R ", C 1-10Alkyl, CO 2CH 3Or OH, R ', R "=H, CH 3, C 2H 5, (CH 3) 2CH, (CH 3) 3C ,-(CH 2) 2-,-(CH 2) 3-,-(CH 2) 4-,-(CH 2) 5-,
Figure C9411392900025
Or , R 4=H, C 2H 5, CH 3C ≡ C-, HC ≡ C-, CF 3, R 5Or R 6=H, F, Cl, OH, CH 3, CF 3, CH 2=or O, R 3R 5=
Figure C9411392900027
Y=X (CF 2CF 2O) n, CF 3(CF 2) m, X=F, Cl, Br, I, H, n=0,1 or 2, m=0-5.
2. a steroidal enol Polyfluoroalkyl sulfonate compound as claimed in claim 1 is characterized in that described compound is the N-tertiary butyl-3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-androstane-3,5-diene-17 β methane amide.
3. a steroidal enol Polyfluoroalkyl sulfonate compound as claimed in claim 1 is characterized in that described compound is 3-[(5-hydrogen-3-oxo octafluoro pentane) sulfonyloxy]-pregnant steroid-3,5-diene-ketone-20.
4. the preparation method of a steroidal enol Polyfluoroalkyl sulfonate compound as claimed in claim 1; the nitrogenous compound that is included in band lone pair electron on solvent and the nitrogen-atoms exists down; steroidal-3-ketone compound and sulfonylation agent reaction is characterized in that described steroidal-3-ketone compound molecular formula is:
Figure C9411392900031
Wherein Or
Figure C9411392900033
R 1=H or CH 3, R 2=H, CH 3Or C 2H 5, R 3=CONR ' R ",
Figure C9411392900034
, C 1-10Alkyl, CO 2CH 3Or OH, R 4=H, C 2H 5, CH 3C ≡ C-, HC ≡ C-, CF 3, R ', R "=H, CH 3, C 2H 5, (CH 3) 2CH, (CH 3) 3C ,-(CH 2) 2-,-(CH 2) 3-,-(CH 2) 4-,-(CH 2) 5-,
Figure C9411392900035
Or
Figure C9411392900036
R 5Or R 6=H, F, Cl, OH, CH 3, CF 3, CH 2=or O,
Figure C9411392900037
, described sulfonylation agent is YCF 2CF 2SO 3F, wherein Y=X (CF 2CF 2O) n, CF 3(CF 2) m, X=F, Cl, Br, I, H, n=0,1 or 2, m=0-5, the nitrogenous compound mole ratio of band lone pair electron is 1 on described steroidal-3-ketone compound, sulfonylation agent and the nitrogen-atoms: 1-20: 1-20.
5. a preparation method as claimed in claim 4 is characterized in that the nitrogenous compound mole ratio of band lone pair electron on described steroidal-3-ketone compound, sulfonylation agent and the nitrogen-atoms is 1: 2-8: 2-8.
6. preparation method as claimed in claim 4, the nitrogenous compound diethylamine, triethylamine, diisopropylethylamine, trimethylpyridine, the lutidine, 1 that it is characterized in that band lone pair electron on the described nitrogen-atoms, 5-diaza-bicyclo (4,3,0)-nonene-5 or 1,8-diaza-bicyclo (5,4,0) hendecene-7.
7. one kind as claim 4,5 or 6 described preparation methods, it is characterized in that temperature of reaction is 160 ℃ of room temperatures.
8. one kind as claim 4,5 or 6 described preparation methods, it is characterized in that the reaction times is 0.5-20 hour.
9. one kind as claim 4,5 or 6 described preparation methods, it is characterized in that described solvent is polar solvent or aromatic hydrocarbons.
10. purposes as claim 1,2 or 3 described steroidal enol Polyfluoroalkyl sulfonate compounds is characterized in that being used for the intermediate of synthesizing steroid medicine.
CN94113929A 1994-10-08 1994-10-08 Steroalkenol polyfluohydrocarbyl sulfonate compound and its deriv., use and preparing process Expired - Fee Related CN1055930C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN94113929A CN1055930C (en) 1994-10-08 1994-10-08 Steroalkenol polyfluohydrocarbyl sulfonate compound and its deriv., use and preparing process

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN94113929A CN1055930C (en) 1994-10-08 1994-10-08 Steroalkenol polyfluohydrocarbyl sulfonate compound and its deriv., use and preparing process

Publications (2)

Publication Number Publication Date
CN1107478A CN1107478A (en) 1995-08-30
CN1055930C true CN1055930C (en) 2000-08-30

Family

ID=5036890

Family Applications (1)

Application Number Title Priority Date Filing Date
CN94113929A Expired - Fee Related CN1055930C (en) 1994-10-08 1994-10-08 Steroalkenol polyfluohydrocarbyl sulfonate compound and its deriv., use and preparing process

Country Status (1)

Country Link
CN (1) CN1055930C (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005007668A1 (en) * 2003-07-16 2005-01-27 Shanhghai Institute Of Organic Chemistry, Chinese Academy Of Sciences A production process for 16-dehydropregnenoneol and its analogs

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1061985C (en) * 1996-04-03 2001-02-14 中国科学院上海有机化学研究所 Method for preparation of progestol by degradation of steroidal saponin

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0231671A1 (en) * 1985-12-26 1987-08-12 Mitsubishi Kasei Corporation Gonatriene derivatives and process for preparing them
US4753932A (en) * 1985-01-14 1988-06-28 Roussel Uclaf Novel 10-substituted steroids

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4753932A (en) * 1985-01-14 1988-06-28 Roussel Uclaf Novel 10-substituted steroids
EP0231671A1 (en) * 1985-12-26 1987-08-12 Mitsubishi Kasei Corporation Gonatriene derivatives and process for preparing them

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005007668A1 (en) * 2003-07-16 2005-01-27 Shanhghai Institute Of Organic Chemistry, Chinese Academy Of Sciences A production process for 16-dehydropregnenoneol and its analogs

Also Published As

Publication number Publication date
CN1107478A (en) 1995-08-30

Similar Documents

Publication Publication Date Title
JP4275747B2 (en) Method for synthesizing fluorinated nitrile compounds
EP1300386B1 (en) Method for producing fluorine-containing compound
RU2279422C2 (en) Method for production of fluorinated ketone
JPH062691B2 (en) Trifluoroethanol manufacturing method
CN1055930C (en) Steroalkenol polyfluohydrocarbyl sulfonate compound and its deriv., use and preparing process
EP0891962B1 (en) Process for the preparation of fluorinated dicarbonyl compounds
JPH11507938A (en) Method for producing ester
CN108707096B (en) Process for preparing aminoalcohol derivatives
JP2001525386A (en) Production of 1,3-propanediol esters
CN112521278B (en) Method for preparing carboxylic ester compound
JPS6097933A (en) Purification of alkanoic acid ester
CN110330456B (en) Synthetic method of 2,2, 2-trifluoroethyl substituted phenanthridine compound
JPS62294643A (en) Novel manufacture of methyl 2,2-dimethyl-3-(2'-methylpropenyl)cyclopropane-1, 1-dicarboxylate
CN110267967B (en) 15-ketosteroid compounds and process for preparing same
CN117756727A (en) Synthesis method of C3-fluoroalkyl substituted quinoxalinone derivative
Fukushi et al. Lewis Acid-Catalyzed Selective Mono-fluorination of Malonates Using Me-NFSI
VERBIT The Synthesis of Alcohols-OD
US7026504B2 (en) Process for preparing alkyladamantyl esters and compositions
JP4709369B2 (en) Esters and their synthesis
JPH0386840A (en) Production of alpha,beta-unsaturated carbonyl compound
CN117843519A (en) Preparation of difluoro ketene and method for converting difluoro ketene into difluoro acetate and difluoro acetate amide
RU2248346C2 (en) Fluorine-containing compound production process
CN118772145A (en) Diazabicyclooctene Process for the preparation of compounds
JPS62207228A (en) Production of fluorine-substituted carbonyl compound
CN1114309A (en) Process for producing carotene compounds

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
C14 Grant of patent or utility model
GR01 Patent grant
C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee