CN102399162B - Method for synthesizing chloramphenicol from 4-chloro-benzaldehyde - Google Patents
Method for synthesizing chloramphenicol from 4-chloro-benzaldehyde Download PDFInfo
- Publication number
- CN102399162B CN102399162B CN 201110432047 CN201110432047A CN102399162B CN 102399162 B CN102399162 B CN 102399162B CN 201110432047 CN201110432047 CN 201110432047 CN 201110432047 A CN201110432047 A CN 201110432047A CN 102399162 B CN102399162 B CN 102399162B
- Authority
- CN
- China
- Prior art keywords
- chloro
- phenyl
- ammediol
- nitro
- chiral catalyst
- 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.)
- Active
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for synthesizing a broad spectrum antibiotic, namely, chloramphenicol. The method comprises the following steps of: synthesizing (1R,2R)-2-nitro-1-(4-chlorophenyl)-1,3-propanediol by using 4-chlorobenzaldehyde and 2-nitroethylalcohol as raw materials in the presence of a chiral catalyst, and performing catalytic hydrogenation to obtain (1R,2R)-2-amino-1-(4-chlorophenyl)-1,3-propanediol; and performing dichloro acetylization and nitro substitution on the intermediate to obtain the chloramphenicol. By the method, the common chiral resolution and aluminum isopropoxide reduction in the industry at present can be avoided, three wastes are reduced, and the raw materials and reagents are cheap and readily available; 4-chlorobenzaldehyde is selected as a raw material, nitro substitution is adopted, and the generation of byproducts in nitration reaction is reduced; moreover, the method comprises a few synthesizing steps, the yield is high, and the method is more suitable for industrial production.
Description
Technical field
The present invention relates to a kind of preparation method of compound, be specifically related to a kind of method by 4-chlorobenzaldehyde synthesizing chloramphenicol.
Background technology
Catilan is broad-spectrum antibiotics, is mainly used in Corynebacterium diphtheriae, and dysentery bacterium, meningococcus, pneumococcal infection also can be used for rickettsial infection.Although it has many side effects as suppressing the marrow hemopoiesis function, cause granular cell and thrombocytopenia or aplastic anemia, but still be the choice drug for the treatment of typhoid fever.
Paraxin is white or little yellowish green needle-like, the crystallization of lengthy motion picture shape or crystalline powder be with.Bitter.149～153 ℃ of fusing points.Be soluble in methyl alcohol, ethanol and acetone and other organic solvent, be slightly soluble in water.Specific optical rotation [α]
D 25=+18.5～+ 21.5 ° (dehydrated alcohol).
Synthetic route report about paraxin has a lot; but the domestic main synthesis technique that puts into production is to be starting raw material with ethylbenzene at present; through oxidation, nitrated, bromination, ammonification, acetylize; the reduction of aldol condensation, aluminum isopropylate, chiral separation, polystep reaction such as two chloroacetylations makes paraxin then.Operational path is as follows:
As can be seen from the above, the synthetic route of paraxin is long at present, because the highest yield of theory that splits has only 50%, calculate with ethylbenzene, domestic production is yield about 30% in fact, make production cost and the three wastes increase, the aluminum isopropylate reduction process also produces and is difficult to the three wastes handled in a large number, and therefore seeking more economical synthetic method is a challenge all the time.
Summary of the invention
Purpose of the present invention is exactly for the synthetic of paraxin provides a kind of raw material to be easy to get, and avoids splitting, and cost is low, the preparation method that yield is high.
Preparation method of the present invention is as follows:
Be starting raw material with the 4-chloro-benzaldehyde; through carrying out asymmetric Henry reaction with the 2-nitroethyl alcohol; obtain (1R; 2R)-2-nitro-1-(4-chloro-phenyl-)-1; ammediol (II); catalytic hydrogenation is with the amino (1R that gets of nitroreduction then; 2R)-and 2-amino-1-(4-chloro-phenyl-)-1, ammediol (III), we found through experiments; with (1R; 2R)-2-amino-1-(4-chloro-phenyl-)-1, the amino of ammediol through two chloroacetylations get (1R, 2R)-2-dichloro acetamide base-1-(4-chloro-phenyl-)-1; ammediol (IV) is then at three (dibenzalacetone) two palladium [Pd
2(dba)
3] under the catalysis with Sodium Nitrite react paraxin (I), like this, we just with the synthetic route control of paraxin at four-step reaction.Crude product can obtain product, HPLC purity＞98.0% with high yield through recrystallization.Operational path is as follows:
Starting raw material also can be 4-bromobenzaldehyde, 4-benzaldehyde iodine.
The structure of catalyst ligand is as follows:
Document (Ma, K. are pressed in its preparation; You, J.Chem.Eur.J.2007,13,1863) method.
Obtained paraxin purity is greater than 98.0% according to the present invention, total recovery about 60%.Method yield height of the present invention, product purity meets the requirements, and can easily realize suitability for industrialized production, is a kind of preparation method that good suitability for industrialized production is worth that has.It is embodied in:
1) raw material is easy to get and is inexpensive.
2) synthetic route is short, though document (Loncaric, C.; Wulff, W.D.Org.Lett., 2001,3675) reported that four of paraxin went on foot synthetic routes, but agents useful for same has paranitrobenzaldehyde, benzylamine and ethyl diazoacetate, and price is relatively costly, also has certain risk.
3) avoid fractionation in the synthetic route and the use of aluminum isopropylate reductive agent, solved a large amount of three wastes problems in the suitability for industrialized production.
4) total recovery height, total recovery is about 67%, is higher than 30% of existing technology far away.
What the present invention had innovation most is: the nitration reaction on the phenyl ring is very complicated, often nitro does not have last to the position that needs, what perhaps obtain is many nitro-compounds, the present invention is at (1R, 2R)-2-dichloro acetamide base-1-(4-chloro-phenyl-)-1, in the nitration reaction of ammediol, three (dibenzalacetone) two palladium [Pd have been adopted
2(dba)
3] make catalyzer, Sodium Nitrite is nitrating agent, and nitration reaction is accurately located, and what reaction obtained substantially is paraxin.
A kind of synthetic method as the described paraxin of structural formula I of the present invention: by (1R, 2R)-2-dichloro acetamide base-1-(4-chloro-phenyl-)-1, ammediol and Sodium Nitrite obtain paraxin through the nitro substitution reaction.
Structural formula I
(1R, 2R)-2-amino-1-(4-chloro-phenyl-)-1, ammediol through two chloroacetylations get (1R, 2R)-2-dichloro acetamide base-1-(4-chloro-phenyl-)-1, ammediol.
(1R, 2R)-2-nitro-1-(4-chloro-phenyl-)-1, ammediol through the catalytic hydrogenation reduction obtain (1R, 2R)-2-amino-1-(4-chloro-phenyl-)-1, ammediol.
Be raw material with starting raw material 4-chloro-benzaldehyde and 2-nitroethyl alcohol, and synthetic obtaining in the presence of chiral catalyst (1R, 2R)-2-nitro-1-(4-chloro-phenyl-)-1, ammediol, starting raw material also can be 4-bromobenzaldehyde, 4-benzaldehyde iodine.
The nitro substitution reaction is with three (dibenzalacetone) two palladium [Pd
2(dba)
3] or palladium trifluoroacetate (Pd (OTFA)
2) be catalyzer, under participating in, the phosphorus part carries out.
Catalytic hydrogenation is catalyzer with palladium carbon, preferentially selects 10% palladium carbon for use.
Chiral catalyst is prepared in dioxane with the chiral catalyst part by mantoquita or acetic acid rhodium.
Mantoquita comprises cupric chloride and copper trifluoromethanesulfcomposite (Cu (OTf)
2), the chiral catalyst part is 2,6-two [(S)-4-sec.-propyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl] pyridine,
The phosphorus part comprises: 2-(di-t-butyl phosphine)-2 ', 4 ', 6 '-tri isopropyl biphenyl (t-BuXPhos), 2-di-t-butyl phosphorus-3,4,5,6-tetramethyl--2 ', 4 ', 6 '-tri isopropyl biphenyl, 2-di-t-butyl phosphorus-3,5-dimethoxy-2 ', at least a in 4 ', 6 '-tri isopropyl biphenyl (t-BuBrettPhos).(document J.AM.CHEM.SOC.209,131,12898-12899)
Embodiment
The following example is used for further narration the present invention, but it is not any restriction to scope of the present invention.The purity testing of each compound is measured at the HP1100 high performance liquid chromatograph.
Embodiment 1 (1R, 2R)-2-nitro-1-(4-chloro-phenyl-)-1,1 of the preparation of ammediol
With 1.8 gram Cu (OTf)
2(0.50mmol), 2.4 grams, 2,6-two [(S)-4-sec.-propyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl] pyridine (5.2mmol) and 40 milliliter 1, the 4-dioxane adds in 250 milliliters of single port flasks, with keeping nitrogen gas stream constant behind the air of nitrogen replacement the inside, under room temperature, magnetic agitation with the ice bath cooling, adds 7.0 gram 4-chlorobenzaldehydes (50mmol) after 2 hours successively, 45.5 gram 2-nitroethyl alcohol (500mmol) and N-methylmorpholine (0.54 milliliter, 5.0mmol), reaction solution stir about 24 hours in 0～5 ℃ of ice bath, after the thin plate chromatography detected no raw material 4-chlorobenzaldehyde spot, volatile solvent was removed in underpressure distillation then, removed catalyzer by filtered through silica gel, filtrate concentrates to such an extent that product 10.6 restrains, yield 91.8%, it is 93.5%, 1H NMR (acetone-d6) δ that HPLC measures the e.e value: 3.71 (s, 1H), 3.85 (m, 1H), 4.12 (m, 1H), 4.52 (m, 1H), 4.79 (m, 1H), 5.01 (d, J=8.7Hz, 1H), 7.15-7.26 (m, 4H).
Embodiment 2 (1R, 2R)-2-nitro-1-(4-chloro-phenyl-)-1,2 of the preparation of ammediol
With 0.8 gram Cu (OTf)
2(0.50mmol), 0.8 gram acetic acid rhodium, 1.2 grams 2,6-two [(S)-4-sec.-propyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl] pyridine (5.2mmol) and 20 milliliter 1 are in 250 milliliters of single port flasks of 4-dioxane adding, with keeping nitrogen gas stream constant behind the air of nitrogen replacement the inside, under room temperature, magnetic agitation was cooled off with ice bath after 2 hours, add 7.0 gram 4-chlorobenzaldehydes (50mmol) successively, 45.5 gram 2-nitroethyl alcohols (500mmol) and 0.15 restrain picoline, reaction solution stir about 20 hours in 4 ℃ of ice baths, after the thin plate chromatography detected no raw material 4-chlorobenzaldehyde spot, volatile solvent was removed in underpressure distillation then, removed catalyzer by filtered through silica gel, filtrate concentrates to such an extent that product 10.9 restrains, yield 92.8%, it is 94.2%, 1H NMR (acetone-d6) δ that HPLC measures the e.e value: 3.71 (s, 1H), 3.85 (m, 1H), 4.12 (m, 1H), 4.52 (m, 1H), 4.79 (m, 1H), 5.01 (d, J=8.7Hz, 1H), 7.15-7.26 (m, 4H).
Embodiment 3 (1R, 2R)-2-nitro-1-(4-chloro-phenyl-)-1,3 of the preparation of ammediol
With 1.8 gram Cu (OTf)
2(0.50mmol), 2.4 grams, 2,6-two [(S)-4-sec.-propyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl] pyridine (5.2mmol) and 40 milliliter 1, the 4-dioxane adds in 250 milliliters of single port flasks, with keeping nitrogen gas stream constant behind the air of nitrogen replacement the inside, under room temperature, magnetic agitation with the ice bath cooling, adds 6.0 gram 4-bromobenzaldehydes after 2 hours successively, 45.5 gram 2-nitroethyl alcohol (500mmol) and N-methylmorpholine (0.54 milliliter, 5.0mmol), reaction solution stir about 30 hours in 4 ℃ of ice baths, after the thin plate chromatography detected no raw material 4-chlorobenzaldehyde spot, volatile solvent was removed in underpressure distillation then, removed catalyzer by filtered through silica gel, filtrate concentrates to such an extent that product 9.6 restrains, yield 86.2%, it is 92.9%, 1HNMR (acetone-d6) δ that HPLC measures the e.e value: 3.71 (s, 1H), 3.85 (m, 1H), 4.12 (m, 1H), 4.52 (m, 1H), 4.79 (m, 1H), 5.01 (d, J=8.7Hz, 1H), 7.15-7.26 (m, 4H).
Embodiment 4 (1R, 2R)-2-nitro-1-(4-chloro-phenyl-)-1,4 of the preparation of ammediol
With 0.8 gram Cu (OTf)
2(0.50mmol), 0.8 gram acetic acid rhodium, 1.2 grams 2,6-two [(S)-4-sec.-propyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl] pyridine (5.2mmol) and 20 milliliters of ethylene dichloride add in 250 milliliters of single port flasks, and are constant with maintenance nitrogen gas stream behind the air of nitrogen replacement the inside, under room temperature, magnetic agitation with the ice bath cooling, adds 6.0 gram 4-benzaldehyde iodines after 2 hours successively, 45.5 gram 2-nitroethyl alcohol (500mmol) and 0.15 gram picoline, reaction solution stir about 20 hours in 4 ℃ of ice baths is behind the no raw material 4-chlorobenzaldehyde spot of thin plate chromatography detection, volatile solvent is removed in underpressure distillation then, remove catalyzer by filtered through silica gel, filtrate concentrates to such an extent that product 10.9 restrains yield 91.6%, it is 93.7% that HPLC measures the e.e value, 1H NMR (acetone-d6) δ: 3.71 (s, 1H), 3.85 (m, 1H), 4.12 (m, 1H), 4.52 (m, 1H), 4.79 (m, 1H), 5.01 (d, J=8.7Hz, 1H), and 7.15-7.26 (m, 4H).
Embodiment 5 (1R, 2R)-2-amino-1-(4-chloro-phenyl-)-1, the preparation of ammediol
With 5.8 gram (1R, 2R)-2-nitro-1-(4-chloro-phenyl-)-1, the preparation of ammediol (25mmol) is dissolved in 100 ml methanol, add 0.1 gram, 10% palladium carbon catalyst, catalytic hydrogenation under hydrogen pressure 0.2MPa, the thin plate chromatography detects no raw material spot after-filtration and removes catalyzer, and filtrate concentrates the back and gets product 4.6 grams with 1: 2.5 ethanol-acetone mixed solvent recrystallization, yield 92.0%
1H?NMR(acetone-d
6)δ：3.45(m，1H)，3.72(s，1H)，3.92(m，1H)，4.17-4.22(m，2H)，4.82(m，1H)，5.05(d，J＝9.0Hz，1H)，5.02-5.09(m，1H)，7.18-7.31(m，4H)。
Embodiment 6 (1R, 2R)-2-dichloro acetamide base-1-(4-chloro-phenyl-)-1, the preparation of ammediol
With 4.5 grams (22mmol) (1R, 2R)-2-amino-1-(4-chloro-phenyl-)-1, ammediol and 30 milliliters of methyl dichloroacetates (0.3mol) add in the single port flask successively, in 100～110 ℃ of stirrings 2 hours, concentrating under reduced pressure behind the no raw material spot of thin plate chromatography detection, solid gets (1R with ethyl acetate and normal hexane mixed solvent recrystallization, 2R)-and 2-dichloro acetic acid formamido--1-(4-chloro-phenyl-)-1, ammediol 6.1 grams, yield 88.7%, 1H NMR (acetone-d6) δ: 3.74 (s, 1H), 3.91 (m, 1H), 4.19 (m, 1H), 4.22 (m, 1H), 4.75 (m, 1H), 5.01 (d, J=8.7Hz, 1H), 6.28 (s, 1H), 7.22-7.40 (m, 4H), 7.65 (s, 1H).
1 of the preparation of embodiment 7 paraxin
With 6 grams (1R, 2R)-2-dichloro acetamide base-1-(4-chloro-phenyl-)-1, ammediol (19mmol), 2.6 gram (38mmol) Sodium Nitrites, 0.09 gram (0.1mmol) three (dibenzalacetone), two palladium [Pd
2(dba)
3], 0.10 gram 2-(di-t-butyl phosphine)-2 ', 4 ', 6 '-tri isopropyl biphenyl (t-BuXPhos), the 45ml trimethyl carbinol add in the 100ml there-necked flask, 105～110 ℃ of reactions added in the single port flask in 10 hours, stirred 2 hours in 100～110 ℃, concentrating under reduced pressure behind the no raw material spot of thin plate chromatography detection, reaction solution concentrates,, concentrate catalyst separating with silicagel column, solid gets paraxin 5.4 grams with ethyl acetate and normal hexane mixed solvent recrystallization, yield 88%, m.p.147～149 °, purity 98.6%, nuclear magnetic spectrum is consistent with standard diagram.
2 of the preparation of embodiment 8 paraxin
With 6 grams (1R, 2R)-2-dichloro acetamide base-1-(4-chloro-phenyl-)-1, ammediol (19mmol), 2.6 gram (38mmol) Sodium Nitrites, 0.05 gram (0.1mmol) palladium trifluoroacetate (Pd (OTFA)
2), 0.08 gram 2-di-t-butyl phosphorus-3,4,5,6-tetramethyl--2 ', 4 ', 6 '-tri isopropyl biphenyl, the 45ml trimethyl carbinol add in the 100ml there-necked flask, and 105～110 ℃ of reactions added in the single port flask in 10 hours, stirred 2 hours in 100～110 ℃, the thin plate chromatography detects concentrating under reduced pressure behind the no raw material spot, and reaction solution is concentrated, with silicagel column with catalyst separating, concentrate, solid gets paraxin 5.5 gram with ethyl acetate and normal hexane mixed solvent recrystallization, yield 89%, m.p.147～149 °, purity 98.7%, nuclear magnetic spectrum is consistent with standard diagram.
Claims (5)
1. synthetic method as the described paraxin of structural formula I is characterized in that ammediol and Sodium Nitrite obtain paraxin through the nitro substitution reaction by (1R, 2R)-2-dichloro acetamide base-1-(4-chloro-phenyl-)-1;
Structural formula I
Wherein, the nitro substitution reaction is with three (dibenzalacetone) two palladium [Pd
2(dba)
3] be catalyzer or palladium trifluoroacetate (Pd (OTFA)
2) be catalyzer, under participating in, the phosphorus part carries out; The phosphorus part is 2-(di-t-butyl phosphine)-2 ', 4 ', 6 '-tri isopropyl biphenyl (t-BuXPhos), 2-di-t-butyl phosphorus-3,4,5,6-tetramethyl--2', 4', the 6'-tri isopropyl biphenyl, 2-di-t-butyl phosphorus-3,5-dimethoxy-2', 4', at least a in the 6'-tri isopropyl biphenyl (t-BuBrettPhos).
2. method according to claim 1 is characterized in that: (1R, 2R)-2-amino-1-(4-chloro-phenyl-)-1, ammediol gets (1R, 2R)-2-dichloro acetamide base-1-(4-chloro-phenyl-)-1, ammediol through two chloroacetylations.
3. method according to claim 2 is characterized in that: (1R, 2R)-2-nitro-1-(4-chloro-phenyl-)-1, ammediol obtains (1R, 2R)-2-amino-1-(4-chloro-phenyl-)-1, ammediol through the catalytic hydrogenation reduction.
4. method according to claim 3 is characterized in that: be raw material with 4-chloro-benzaldehyde and 2-nitroethyl alcohol, synthetic obtaining in the presence of chiral catalyst (1R, 2R)-2-nitro-1-(4-chloro-phenyl-)-1, ammediol; Chiral catalyst is prepared in dioxane by mantoquita or acetic acid rhodium and chiral catalyst part; Mantoquita is selected from cupric chloride and copper trifluoromethanesulfcomposite (Cu (OTf)
2), the chiral catalyst part is 2,6-two [(S)-4-sec.-propyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl] pyridine.
5. method according to claim 3, it is characterized in that: catalytic hydrogenation is catalyzer with palladium carbon.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110432047 CN102399162B (en) | 2011-12-21 | 2011-12-21 | Method for synthesizing chloramphenicol from 4-chloro-benzaldehyde |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110432047 CN102399162B (en) | 2011-12-21 | 2011-12-21 | Method for synthesizing chloramphenicol from 4-chloro-benzaldehyde |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102399162A CN102399162A (en) | 2012-04-04 |
| CN102399162B true CN102399162B (en) | 2013-09-25 |
Family
ID=45881868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110432047 Active CN102399162B (en) | 2011-12-21 | 2011-12-21 | Method for synthesizing chloramphenicol from 4-chloro-benzaldehyde |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102399162B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108017549A (en) * | 2017-12-07 | 2018-05-11 | 南通常佑药业科技有限公司 | A kind of preparation method of 1- aryl -2- amino -1,3- propanediol hydrochloride derivatives |
| CN110878024B (en) * | 2019-12-11 | 2021-02-26 | 四川大学 | Synthesis method of (1R,2R) -nitroalcohol compound |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB743446A (en) * | 1952-08-22 | 1956-01-18 | Boehringer & Soehne Gmbh | Improvements in or relating to aromatic 2-aminoalkanediols-(1.3) |
| CN101941927A (en) * | 2010-09-28 | 2011-01-12 | 湖北美天生物科技有限公司 | Method for analyzing (1R, 2R)-2-amino-1-(4-(methylsulfonyl)-phenyl)-1,3-propylene glycol as intermediate of florfenicol |
-
2011
- 2011-12-21 CN CN 201110432047 patent/CN102399162B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB743446A (en) * | 1952-08-22 | 1956-01-18 | Boehringer & Soehne Gmbh | Improvements in or relating to aromatic 2-aminoalkanediols-(1.3) |
| CN101941927A (en) * | 2010-09-28 | 2011-01-12 | 湖北美天生物科技有限公司 | Method for analyzing (1R, 2R)-2-amino-1-(4-(methylsulfonyl)-phenyl)-1,3-propylene glycol as intermediate of florfenicol |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102399162A (en) | 2012-04-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3359522B1 (en) | Process for preparation of n-boc biphenyl alaninol | |
| CN102399164B (en) | Method for synthesizing chloramphenicol from nitromethane | |
| CN104447725A (en) | Chiral compound comprising iminopyridyl oxazoline and preparation method thereof | |
| Shi et al. | Ru (II)-catalyzed ortho-amidation and decarboxylation of aromatic acids: a versatile route to meta-substituted N-aryl benzamides | |
| JPWO2009060886A1 (en) | Selective reduction of nitro group by metal catalyst supported carbon | |
| CN102399165B (en) | Method for preparing chloramphenicol from nitromethane | |
| CN102399163B (en) | Method for preparing chloramphenicol from 4-chloro-benzaldehyde | |
| CN105339352A (en) | Process for the stereoselective preparation of a pyrazole-carboxamide | |
| CN102399162B (en) | Method for synthesizing chloramphenicol from 4-chloro-benzaldehyde | |
| CN102399160B (en) | Method for synthesizing chloramphenicol | |
| CN112239436A (en) | Preparation method of 4-acyl-2 (5H) -furanone compound | |
| Wei et al. | Ru-Catalyzed highly diastereoselective hydrogenation of N-tert-butylsulfinyl ketimines for the synthesis of aryl glycine derivatives | |
| CN102391143B (en) | Method for preparing broad-spectrum antibiotic chloramphenicol | |
| CN102285896B (en) | Method for synthesizing broad-spectrum antibiotic chloramphenicol | |
| CN102399161B (en) | Method for preparing chloramphenicol | |
| CN113045503A (en) | Preparation method of 2-trifluoromethyl substituted quinazolinone compound and application of compound in synthesis of drug molecules | |
| CN110483272B (en) | Novel method for asymmetric synthesis of (1S,2S) -2-fluorocyclopropanecarboxylic acid by catalysis of chiral rhodium catalyst | |
| CN112694430B (en) | Preparation method of 1, 5-dihydro-2H-pyrrole-2-ketone compound | |
| CN111978194B (en) | Preparation method of aryl acetamide compound | |
| CN108675950A (en) | A kind of synthetic method of 2- alkenyls Benzazole compounds | |
| CN104086525A (en) | Spiro[tetralone-tetrahydrothiophene] derivative having antibiosis activity, and synthetic method and application thereof | |
| CN110684043B (en) | C-N axis chiral arylamine compound and preparation method thereof | |
| CN114105972A (en) | Xinkening derivative and application thereof in preparation of high-optical-purity indoxacarb intermediate | |
| CN115246786B (en) | Preparation method of indole compound or benzoxazine compound | |
| CN107417623B (en) | Method for synthesizing 5-diarylaminobenzimidazole derivative in one step |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |