CA2134093A1 - Process for the preparation of 3(s)-methylheptanoic acid and intermediates therefor - Google Patents
Process for the preparation of 3(s)-methylheptanoic acid and intermediates thereforInfo
- Publication number
- CA2134093A1 CA2134093A1 CA 2134093 CA2134093A CA2134093A1 CA 2134093 A1 CA2134093 A1 CA 2134093A1 CA 2134093 CA2134093 CA 2134093 CA 2134093 A CA2134093 A CA 2134093A CA 2134093 A1 CA2134093 A1 CA 2134093A1
- Authority
- CA
- Canada
- Prior art keywords
- acid
- methylheptanoic acid
- methylheptanoic
- alpha
- methyl
- 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.)
- Abandoned
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/487—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
3(S)-methylheptanoic acid is prepared by fractional crystallization of the salt of racemic 3-methylheptanoic acid with (S)-.alpha.-methylbenzyl amine followed by acidification.
Description
W O 93/22269 2 1 3 `'~ O ~ 3 PCT/US9~/00726 5PROCESS FOR THE PREPARATION OF 3 (S)-METHYLHEPTANOIC ACID :
AND INTERMEDIATES THEREFOR``
. ~
Backqround of the Invention The present invention is directed to a process and intermediates for the 10manufacture of 3~S)-methylheptanoic acid of the absolute stereochemical formula (I) C H 3~"~H
15~ COOH `,~
;
() I ~
which is a useful interrnediate for the preparation of immunoregulatory agents of the !
20 formula (Il) CH~ H o H ooR4 H OCH~<H
~N4~,N~N ~2R5;
- -H o H
j~ 25 S -- D`-- - D ``
I!!) wherein R4 and R5 are each hydrogen oc one of R4 and Rs j5 hydrogen and the other is (Cl-C6)alkyl or (C0-C3)cycloalkylmethyl as described in copending, commonly owned 30 United States Patent Applications Seriai Nos. 07/346,118, filed February 21, 1989 and 07/3411350 filed February 21, 1989, -which. are herein incorporated by reference.
A procedure used to prepare 3(S)-methylheptanoic acid is described by U.S. I:
Serial No. 07/341,350 as show~beiow.................................... I .
_ WO 93/~2269 P(~/US93/~0~26 21;3i0~3 Imldazole ~ ~ ...s ~ OH ~p `OTBD115 3 -. _ CH2C12/MeOH ~ ~ Ph3PCH3Br DMS 1~ OTBDMS "BuL i d THF
Pd-C~H2 ~ H2CrO4 C 0 2 H ' E i o H ~I C 2 R C e t o n e . .
25 U. S. Serial No-. û7/346,118 describes the synthesis of S-3 -alkylheptanoic acids from a .
trans~alken 3-ol of the fomlula (111) R
.
30 :
_ ~ ~OH
(111) 2.~ .093 WO 93/22269 PCr/US93/0072S :
wherein R is methyl or ethyl which is converted to a compound of the formula (IV) ~.
~H
~"'0 H
(IV) by the action of t-butyl hydroperoxide, in a reaction inert soivent in the presence of titanium tetraisopropoxide and L-(+)-diisopropyl tartrate, in an amount sufficient to oxidize the Sffnantiomer and in a second step, the product of the above reaction is stereospecifically condense~ with a tri~(C,-C3)-alkyl]orthoacetate and, without isolation, ¦
the intermediate allyl-enol ether rearranged, in the presence of an acid in a reaction inert solv~nt, to yield a (Ct-C3)alkyl 3(R)-alkyl~hepenoate of the absolute stereochemical formula (V) R H -;
Jl ~ ~ C O O H
.. - ._ .
.
which may be hydrogenated to the desiréd S-~alkylheptanoic acid.
i Optically pure 3(S)-methylheptanoic acid (l) has been prepared from the corresponding racamate in unspecified yield by- multiple (eight) crystallizations of the quinine salt at an inconvenlently low temperature ot -15C. ~Levene et al., J. Biol.
Chem. 95, pp. 1 24, 1932, at page 18, tliere c~lied 2-n-butylbutyric acid4]. Optically - ac~ve ~methylheptanoic acid has subsequently been produced by a number of other 35 methods ~Soai et al., J. Chem. Soc., Chem. Commun. 1985, pp. 496470; Oppolzer et al., Helv. Chim. Acta. 68, pp. 212-215 (1985); Ohno e~ al., U.S. Patent 4,564,620 (1986);
Mori st al., Synthesis 1982, pp. 752-753; Oppolzer et al., Helva. Chim. Acta. 64, pp.
WO g3/222~9 PCI`/US93/~0726 ~ 1 3 ~ O ~ 3 2808-2811 (1981); Mukaiyama et al., Chem. Lett. 1981, pp. 913-916; Posner et al., J.
Am. Chem. Soc 103, pp. 2886-2888 (1981); Mukaiyama et al., Bull. Chem. Soc. Japan, 51, pp. 3368-3372 (1978); Meyers et al., J. Am. Chem. Soc. 98, pp. 2290-2294 (1976)].
The above described preparations generally suffer from one or more 5 disadvantages: the product acid is not optically pure, the reaction temperatures are inconveniently low, between -78C and -30C, use of organometallic reagents, which are dfflicult to handle on a large scale, is required, overall yields are low; and/or the required reagents are not readily available.
Summarv of the Invention This invention relates to a novel process for the preparation of 3~S)-rnethylheptanoic acid which comprises the sequential steps of;
(a) reaction of racemic 3-methylheptanoic acid with (S)--methylbenzyl amine to form a mixtura of diastereomeric salts;
(b) separation of the diastereomeric salts from step (a) by recrystallization to yield (S)--methylbenzylammonium 3~S)-methylheptanoate;
(c) conversion of said (S)-~-rnethylbenzylammonium 3(S)-methyl heptanoate of step (b) to 3(S)-methylheptanoic acid by treatment with acid.
In another aspect, this invention relates to the use of acetonitrile as the recrystallizing solvent in step (b).
In yet ~another~ aspect this invention relates to the compound (S)- -methylbenzylammonium 3(S)-methylheptanoate.
In yet another-aspect this invention comprises a process for preparation of 3(S)-methylheptanoic acid- from an~ enriched mixture of 3R and 3S-methylheptanoic acid which contains a preponderance of the (S) isomer. Such an enriched mixture containing about 70h 3(S)-methylheptanoic acid is available from the procedure of Meyers,- at al., J. ~m. Chem. Soc., 98, 2290-2294, (1976).
.
- ~ _ ~ Detailed DescriDtion of the Invention 30 As used here, the expression ~reaction inert solvent~ refers to a solvent system in which the components do not react with starting materials, reagents, intermediates or products in a manner which adversely affects the yield or purity of the desired product.
wo g3/2æ69 ~ ~ 3 i ~ n ~ Pcr/uss3/on72~
~ acemic 3-methylheptanoic acid is readily available by the procedure of Organic Synthesis, Coll. Vol. 5, 762-766, (John Wiley ~ Sons, 1973) which is herein incorporated by reference.
(S~- ~ rrlethylbenzyiamine is available from the Aldrich Chemical Co., Milwaukee, 5 Wl 53233.
Racemic 3-methylheptanoic acid is dissolved in a reaction inert solvent and an approximate molar amount of (S)- methylbenzylamine is added slowly. The choiceof solvent is not critical, but it was found that the diastereomeric salt readily precipitates from acetonitrile which is the preferred solvent. The temperature of the salt formation 10 is not critical, but rorm temperature was found to be convenient and is preferred.
The diastereomeric salt of race~,nic 3-methylheptanoic acid and (S)- -methylbenzylamine is purified by recrystallization to isolate the desired (S)- -methylbenzy.ammonium (S)-3-methylheptanoate which is generally less soluble than the other diastereomzric sa~t i.e., R-acid/S-amine. ~ ~tonitrile is the preferred solvent for 15 recrystallization. Multiple recrystallizations may be required to obtain the required optica purity and three crystallizations were found to yield a 98% optically pure product.
It was found to be convenient to dissolve the sal$ in boiling solvent and cool slowly over several hours until the product has precipitated. 3(S)-methylheptanoic acid is obtained from the salt by acidification of a solution of the salt with strong acid at room 20 temperature. The temperature, solvent and acid are not critical. Any strong mineral acid is effective; hydrochloric acid is preferred. The preferred solvent is a tv.~o phase system employing n~hexanes or ethylacetate and wate.-, but any reaction inert solvent system wou.ld be acceptable. -The fr.llowing examples are provided solely for the pwpose of~fu.ther illustration 25 and are not intended to limit the invention which is defined by the claims.
., Example~
Preparation of the Diastereomeric Sa.t of 3-Methylheptanoic Acid and (S)--Methyl .
Benzylamine _ ~ - F--30 A solution of racemic 3-methylheptarloic acid (3.1 g, 21.5 mmol) in acetonitrile (20 mL) was treated with dropwise addition of (S)--methylbenzylamine (2.8 mL, 21.5 mmol).
White solid was obsen~ed to precipitate, and the resulting white suspension was stirred at room temperature for 3.5 hours. The white solid was collected by suction filtration WO 93/22269 PCI~US93~0~726 213 Ll ~ 9 3 and dried in vacuum (house vacuum, 48C) overnight. 4.65 g of the diastereomericsalt was obtained (82% yield).
Example 2 5 Recrystallization of the Diastereomeric Salt; (S)- -methylbenzylammonium 3(S)-methylheDtanoate _ _ _ A slurry of the 3-methylheptanoic acid/(S)--methylbenzylamine salt (30 9) from Example 1 in acetonitrile (300 mL) was stirred mechanically under nitrogen and heated with an oil bath until complete dissolution was observed. The solution was allowed to 10 cool slowly as white solid precipitated. The resulting suspension was stirred overnight and the white solid was collected by suction filtration. After drying in a vacuum oven, 20.77 g of salt was obtained (37% ee by rotation, [ ~ 11.27, C-5.05,CHCI3). The above procedure was repeated twice to provide 10.98 g of the salt (73% yield of ' theoretical). The optical purity was judged to be 97%ee ([1~ =-13.66, C=5.05, 15 CHCI3) by comparing the rotations of diastereomeric salts from optically pure acid prepared by the method of U.S. Serial No. 07/341,350 and the title compound.
Example 3 3(S)-Methvlheptanoic Acid 20 A. The salt from Example 2 (1.59 g, 5.99 mmol) in a mixture of ethyl acetate (20 - mL) and water-(-10 mL)-was treated with 1N HCI (10 mL) and stirred at room temperature for 1.25 hours. The aqueous layer was separated from the organic andextracted with ethyl acetate ~2QmL). The organic layer and extract were combined, I
washed with water (1 Q m'L)'and then brine. After drying over sodium sulfate, the solvent 25 was removed to provide the acid as a colorless oil in quantitative yield.
B. I The salt from Exarnple 2 (1.0 9, 3.77 mmol) in a mixture of n-hexanes (10 mL) and water (5 mL) was treated with 1 N HCI (5 mL) and stirred at room temperature for 3.5 hours. The aqueous layer (pH-1) was separated from the organic and extractedwith n-hexanes (2x20'rnL). The organic layer and extracts were combined, washed with ' 30 water (10 mL) and then brine. After drying over sodium sulfate, the solvent was removed to provide the acid as a colorless oil (0.54 9, 99.4% yield). '
AND INTERMEDIATES THEREFOR``
. ~
Backqround of the Invention The present invention is directed to a process and intermediates for the 10manufacture of 3~S)-methylheptanoic acid of the absolute stereochemical formula (I) C H 3~"~H
15~ COOH `,~
;
() I ~
which is a useful interrnediate for the preparation of immunoregulatory agents of the !
20 formula (Il) CH~ H o H ooR4 H OCH~<H
~N4~,N~N ~2R5;
- -H o H
j~ 25 S -- D`-- - D ``
I!!) wherein R4 and R5 are each hydrogen oc one of R4 and Rs j5 hydrogen and the other is (Cl-C6)alkyl or (C0-C3)cycloalkylmethyl as described in copending, commonly owned 30 United States Patent Applications Seriai Nos. 07/346,118, filed February 21, 1989 and 07/3411350 filed February 21, 1989, -which. are herein incorporated by reference.
A procedure used to prepare 3(S)-methylheptanoic acid is described by U.S. I:
Serial No. 07/341,350 as show~beiow.................................... I .
_ WO 93/~2269 P(~/US93/~0~26 21;3i0~3 Imldazole ~ ~ ...s ~ OH ~p `OTBD115 3 -. _ CH2C12/MeOH ~ ~ Ph3PCH3Br DMS 1~ OTBDMS "BuL i d THF
Pd-C~H2 ~ H2CrO4 C 0 2 H ' E i o H ~I C 2 R C e t o n e . .
25 U. S. Serial No-. û7/346,118 describes the synthesis of S-3 -alkylheptanoic acids from a .
trans~alken 3-ol of the fomlula (111) R
.
30 :
_ ~ ~OH
(111) 2.~ .093 WO 93/22269 PCr/US93/0072S :
wherein R is methyl or ethyl which is converted to a compound of the formula (IV) ~.
~H
~"'0 H
(IV) by the action of t-butyl hydroperoxide, in a reaction inert soivent in the presence of titanium tetraisopropoxide and L-(+)-diisopropyl tartrate, in an amount sufficient to oxidize the Sffnantiomer and in a second step, the product of the above reaction is stereospecifically condense~ with a tri~(C,-C3)-alkyl]orthoacetate and, without isolation, ¦
the intermediate allyl-enol ether rearranged, in the presence of an acid in a reaction inert solv~nt, to yield a (Ct-C3)alkyl 3(R)-alkyl~hepenoate of the absolute stereochemical formula (V) R H -;
Jl ~ ~ C O O H
.. - ._ .
.
which may be hydrogenated to the desiréd S-~alkylheptanoic acid.
i Optically pure 3(S)-methylheptanoic acid (l) has been prepared from the corresponding racamate in unspecified yield by- multiple (eight) crystallizations of the quinine salt at an inconvenlently low temperature ot -15C. ~Levene et al., J. Biol.
Chem. 95, pp. 1 24, 1932, at page 18, tliere c~lied 2-n-butylbutyric acid4]. Optically - ac~ve ~methylheptanoic acid has subsequently been produced by a number of other 35 methods ~Soai et al., J. Chem. Soc., Chem. Commun. 1985, pp. 496470; Oppolzer et al., Helv. Chim. Acta. 68, pp. 212-215 (1985); Ohno e~ al., U.S. Patent 4,564,620 (1986);
Mori st al., Synthesis 1982, pp. 752-753; Oppolzer et al., Helva. Chim. Acta. 64, pp.
WO g3/222~9 PCI`/US93/~0726 ~ 1 3 ~ O ~ 3 2808-2811 (1981); Mukaiyama et al., Chem. Lett. 1981, pp. 913-916; Posner et al., J.
Am. Chem. Soc 103, pp. 2886-2888 (1981); Mukaiyama et al., Bull. Chem. Soc. Japan, 51, pp. 3368-3372 (1978); Meyers et al., J. Am. Chem. Soc. 98, pp. 2290-2294 (1976)].
The above described preparations generally suffer from one or more 5 disadvantages: the product acid is not optically pure, the reaction temperatures are inconveniently low, between -78C and -30C, use of organometallic reagents, which are dfflicult to handle on a large scale, is required, overall yields are low; and/or the required reagents are not readily available.
Summarv of the Invention This invention relates to a novel process for the preparation of 3~S)-rnethylheptanoic acid which comprises the sequential steps of;
(a) reaction of racemic 3-methylheptanoic acid with (S)--methylbenzyl amine to form a mixtura of diastereomeric salts;
(b) separation of the diastereomeric salts from step (a) by recrystallization to yield (S)--methylbenzylammonium 3~S)-methylheptanoate;
(c) conversion of said (S)-~-rnethylbenzylammonium 3(S)-methyl heptanoate of step (b) to 3(S)-methylheptanoic acid by treatment with acid.
In another aspect, this invention relates to the use of acetonitrile as the recrystallizing solvent in step (b).
In yet ~another~ aspect this invention relates to the compound (S)- -methylbenzylammonium 3(S)-methylheptanoate.
In yet another-aspect this invention comprises a process for preparation of 3(S)-methylheptanoic acid- from an~ enriched mixture of 3R and 3S-methylheptanoic acid which contains a preponderance of the (S) isomer. Such an enriched mixture containing about 70h 3(S)-methylheptanoic acid is available from the procedure of Meyers,- at al., J. ~m. Chem. Soc., 98, 2290-2294, (1976).
.
- ~ _ ~ Detailed DescriDtion of the Invention 30 As used here, the expression ~reaction inert solvent~ refers to a solvent system in which the components do not react with starting materials, reagents, intermediates or products in a manner which adversely affects the yield or purity of the desired product.
wo g3/2æ69 ~ ~ 3 i ~ n ~ Pcr/uss3/on72~
~ acemic 3-methylheptanoic acid is readily available by the procedure of Organic Synthesis, Coll. Vol. 5, 762-766, (John Wiley ~ Sons, 1973) which is herein incorporated by reference.
(S~- ~ rrlethylbenzyiamine is available from the Aldrich Chemical Co., Milwaukee, 5 Wl 53233.
Racemic 3-methylheptanoic acid is dissolved in a reaction inert solvent and an approximate molar amount of (S)- methylbenzylamine is added slowly. The choiceof solvent is not critical, but it was found that the diastereomeric salt readily precipitates from acetonitrile which is the preferred solvent. The temperature of the salt formation 10 is not critical, but rorm temperature was found to be convenient and is preferred.
The diastereomeric salt of race~,nic 3-methylheptanoic acid and (S)- -methylbenzylamine is purified by recrystallization to isolate the desired (S)- -methylbenzy.ammonium (S)-3-methylheptanoate which is generally less soluble than the other diastereomzric sa~t i.e., R-acid/S-amine. ~ ~tonitrile is the preferred solvent for 15 recrystallization. Multiple recrystallizations may be required to obtain the required optica purity and three crystallizations were found to yield a 98% optically pure product.
It was found to be convenient to dissolve the sal$ in boiling solvent and cool slowly over several hours until the product has precipitated. 3(S)-methylheptanoic acid is obtained from the salt by acidification of a solution of the salt with strong acid at room 20 temperature. The temperature, solvent and acid are not critical. Any strong mineral acid is effective; hydrochloric acid is preferred. The preferred solvent is a tv.~o phase system employing n~hexanes or ethylacetate and wate.-, but any reaction inert solvent system wou.ld be acceptable. -The fr.llowing examples are provided solely for the pwpose of~fu.ther illustration 25 and are not intended to limit the invention which is defined by the claims.
., Example~
Preparation of the Diastereomeric Sa.t of 3-Methylheptanoic Acid and (S)--Methyl .
Benzylamine _ ~ - F--30 A solution of racemic 3-methylheptarloic acid (3.1 g, 21.5 mmol) in acetonitrile (20 mL) was treated with dropwise addition of (S)--methylbenzylamine (2.8 mL, 21.5 mmol).
White solid was obsen~ed to precipitate, and the resulting white suspension was stirred at room temperature for 3.5 hours. The white solid was collected by suction filtration WO 93/22269 PCI~US93~0~726 213 Ll ~ 9 3 and dried in vacuum (house vacuum, 48C) overnight. 4.65 g of the diastereomericsalt was obtained (82% yield).
Example 2 5 Recrystallization of the Diastereomeric Salt; (S)- -methylbenzylammonium 3(S)-methylheDtanoate _ _ _ A slurry of the 3-methylheptanoic acid/(S)--methylbenzylamine salt (30 9) from Example 1 in acetonitrile (300 mL) was stirred mechanically under nitrogen and heated with an oil bath until complete dissolution was observed. The solution was allowed to 10 cool slowly as white solid precipitated. The resulting suspension was stirred overnight and the white solid was collected by suction filtration. After drying in a vacuum oven, 20.77 g of salt was obtained (37% ee by rotation, [ ~ 11.27, C-5.05,CHCI3). The above procedure was repeated twice to provide 10.98 g of the salt (73% yield of ' theoretical). The optical purity was judged to be 97%ee ([1~ =-13.66, C=5.05, 15 CHCI3) by comparing the rotations of diastereomeric salts from optically pure acid prepared by the method of U.S. Serial No. 07/341,350 and the title compound.
Example 3 3(S)-Methvlheptanoic Acid 20 A. The salt from Example 2 (1.59 g, 5.99 mmol) in a mixture of ethyl acetate (20 - mL) and water-(-10 mL)-was treated with 1N HCI (10 mL) and stirred at room temperature for 1.25 hours. The aqueous layer was separated from the organic andextracted with ethyl acetate ~2QmL). The organic layer and extract were combined, I
washed with water (1 Q m'L)'and then brine. After drying over sodium sulfate, the solvent 25 was removed to provide the acid as a colorless oil in quantitative yield.
B. I The salt from Exarnple 2 (1.0 9, 3.77 mmol) in a mixture of n-hexanes (10 mL) and water (5 mL) was treated with 1 N HCI (5 mL) and stirred at room temperature for 3.5 hours. The aqueous layer (pH-1) was separated from the organic and extractedwith n-hexanes (2x20'rnL). The organic layer and extracts were combined, washed with ' 30 water (10 mL) and then brine. After drying over sodium sulfate, the solvent was removed to provide the acid as a colorless oil (0.54 9, 99.4% yield). '
Claims (4)
1. A process for the preparation of 3(S)-methylheptanoic acid which comprises the sequential steps of:
(a) reaction of racemic 3-methylheptanoic acid with (S)-.alpha.-methyl benzylamine to form a mixture of diastereomeric salts;
(b) separation of the diastereomeric salts from step (a) by recrystallization to yield (S)-.alpha.-methyl benzylammonium 3(S)-methylheptanoate;
(c) conversion of said (S)-.alpha.-methyl benzylammonium 3(S)-methyl heptanoate of step (b) to 3(S)-methylheptanoic acid by treatment with acid.
(a) reaction of racemic 3-methylheptanoic acid with (S)-.alpha.-methyl benzylamine to form a mixture of diastereomeric salts;
(b) separation of the diastereomeric salts from step (a) by recrystallization to yield (S)-.alpha.-methyl benzylammonium 3(S)-methylheptanoate;
(c) conversion of said (S)-.alpha.-methyl benzylammonium 3(S)-methyl heptanoate of step (b) to 3(S)-methylheptanoic acid by treatment with acid.
2. The process of claim 1 in which said recrystallization of step (b) is accomplished using acetonitrile as solvent.
3. The compound (S)-.alpha.-methylbenzyl ammonium 3-(S)-methylheptanoate.
4. A process for the separation of 3(S)-methylheptanoic acid from a mixture of 3(S)- and 3(R)-methylheptanoic acids which contains a preponderance of 3(S)-methylheptanoic acid which comprises the sequential steps of:
(a) reaction of said mixture of 3-methylheptanoic acids with (S)-.alpha.-methylbenzylamine to form a mixture of diastereomeric salt;
(b) separation of the diastereomeric salts from step (a) by recrystallization to yield (S)-.alpha.-methyl benzylammonium 3(S)-methylheptanoate;
(c) conversion of said (S)-.alpha.-methyl benzylammonium 3(S)-methyl heptanoate of step (b) to 3(S)-methylheptanoic acid by treatment with acid.
(a) reaction of said mixture of 3-methylheptanoic acids with (S)-.alpha.-methylbenzylamine to form a mixture of diastereomeric salt;
(b) separation of the diastereomeric salts from step (a) by recrystallization to yield (S)-.alpha.-methyl benzylammonium 3(S)-methylheptanoate;
(c) conversion of said (S)-.alpha.-methyl benzylammonium 3(S)-methyl heptanoate of step (b) to 3(S)-methylheptanoic acid by treatment with acid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87756492A | 1992-05-01 | 1992-05-01 | |
| US877,564 | 1992-05-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2134093A1 true CA2134093A1 (en) | 1993-11-11 |
Family
ID=25370235
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2134093 Abandoned CA2134093A1 (en) | 1992-05-01 | 1993-02-02 | Process for the preparation of 3(s)-methylheptanoic acid and intermediates therefor |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0638059A1 (en) |
| JP (1) | JPH07502538A (en) |
| CA (1) | CA2134093A1 (en) |
| FI (1) | FI945119A0 (en) |
| WO (1) | WO1993022269A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19501452A1 (en) * | 1995-01-19 | 1996-07-25 | Basf Ag | Process for the production of optically active 2-halopropionic acids |
| DE102004025901A1 (en) | 2004-05-27 | 2005-12-22 | Consortium für elektrochemische Industrie GmbH | Process for the preparation of optically active 3-alkylcarboxylic acids |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB957990A (en) * | 1961-03-14 | 1964-05-13 | Merck & Co Inc | Salts of substituted indoles |
| SE363818B (en) * | 1968-08-15 | 1974-02-04 | Lilly Co Eli | |
| FR2262652A1 (en) * | 1974-02-28 | 1975-09-26 | Rhone Poulenc Ind | Resolving optical isomers of cyclonic dicarboxylic acids - by forming salt with alpha-phenyl ethyl amine enantiomer |
| US4289711A (en) * | 1975-09-05 | 1981-09-15 | Burroughs Wellcome Co. | Ester synthesis |
| JPH0395188A (en) * | 1989-09-08 | 1991-04-19 | Mitsui Petrochem Ind Ltd | Continuous production of dimer alkaloids |
-
1993
- 1993-02-02 JP JP5519230A patent/JPH07502538A/en active Pending
- 1993-02-02 WO PCT/US1993/000726 patent/WO1993022269A1/en not_active Application Discontinuation
- 1993-02-02 EP EP93903682A patent/EP0638059A1/en not_active Withdrawn
- 1993-02-02 CA CA 2134093 patent/CA2134093A1/en not_active Abandoned
-
1994
- 1994-10-31 FI FI945119A patent/FI945119A0/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO1993022269A1 (en) | 1993-11-11 |
| EP0638059A1 (en) | 1995-02-15 |
| FI945119A (en) | 1994-10-31 |
| FI945119A0 (en) | 1994-10-31 |
| JPH07502538A (en) | 1995-03-16 |
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