Process for the preparation of cis-alpha,beta substituted cyclopentanones

Patent metadata

Field	Value
Publication number	US-RE50250-E
Application number	US-201917866170-A
Country	US
Kind code	E1
Filing date	Dec 16, 2019
Priority date	Dec 19, 2018
Publication date	Dec 31, 2024
Grant date	Dec 31, 2024

Abstract

Described herein is a process for the preparation of a mixture of compounds of formula

having a weight ratio of the cis-diastereomers to trans-diastereoisomers higher than 1:1, where R 1 represents a C 1-8 alkyl group, a C 2-8 alkenyl group or a C 2-8 alkynyl group, each optionally substituted with one or two of a C 1-4 alkyl alkoxy ether group and/or a C 1-4 alkyl carboxylester group and R 2 represents a C 1-6 alkyl, a C 2-6 alkenyl or a C 2-6 alkynyl group, each optionally substituted with a C 1-4 alkyl alkoxy ether group, a carboxylic acid group or a C 1-4 alkyl carboxylester group and compounds suitable in the process.

First claim

The invention claimed is:

1. A process for the preparation of a mixture of compounds of formula

having a weight ratio of the cis-diastereomers to trans-diastereomers higher than 1:1,
wherein R 1 represents a C 1-8 alkyl group, a C 2-8 alkenyl group or a C 2-8 alkynyl group, each optionally substituted with one or two of a C 1-4 alkyl alkoxy ether group and/or C 1-4 alkyl carboxylester group, and R 2 represents a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 2-6 alkynyl group, each optionally substituted with an C 1-4 alkyl alkoxy ether group, a carboxylic acid group or a C 1-4 alkyl carboxylester group,
by subjecting a mixture of compounds of formula

having a weight ratio of the cis-diastereomers to trans-diastereomers equal or lower than 1:1,
wherein R 1 and R 2 have the same meaning as indicated above,
to the steps comprising (a) ketal formation, (b) separating the trans-diastereomers and cis-diastereomers and (c) hydrolyzing the ketal of the cis-diastereomers.

2. The process according to claim 1 , wherein R 1 represents a linear C 3-7 alkyl group or a linear C 3-7 alkenyl group or a linear C 3-7 alkynyl group.

3. The process according to claim 1 , wherein R 2 represents a C 1-3 alkyl group optionally substituted with a C 1-3 alkyl carboxylester group.

4. The process according to claim 1 , wherein the compound of formula (I) is methyl-3-oxo-2-pentylcyclopentanacetate, methyl-3-oxo-2-(2-pentenyl)-1-cyclopentaneacetate or (Z)-methyl-3-oxo-2-(2-pentenyl)-1-cyclopentaneacetate.

5. The process according to claim 1 , wherein step (b) is carried out by distillation.

6. The process according to claim 1 , wherein step (a) is carried out in the presence of an acid.

7. The process according to claim 1 , wherein step (a) is carried out in a hydrocarbon solvent.

8. The process according to claim 1 , wherein step (a) is carried out in the presence of a diol of formula HO—C(R 4 )H—(C(R 4 ) 2 ) n —H(R 4 )C—OH wherein n is an integer from 0 to 3 and R 4 , each independently, is a hydrogen or C 1-3 alkyl group.

9. The process according to claim 1 , wherein step (a) is carried out in the presence of ethylene glycol, 1,3-propanediol, 2,3-butanediol, 1,2-propanediol, 2,2-dimethyl-1,3-propanediol, 1,2-butanediol, or 2-methyl-1,3-propanediol.

10. The process according to claim 1 , wherein step (c) is carried out in the presence of an acid.

11. The process according to claim 1 , wherein step (a) is carried out in the presence of H 2 SO 4 , pyridium tosylate, MHSO 4 , wherein M is an alkaline metal, Al 2 (SO 4 ) 3 , heterogeneous solid acid, or alkyl or aryl sulfonic acid.

12. The process according to claim 1 , wherein step (a) is carried out in the presence of KHSO 4 .

13. The process according to claim 1 , wherein step (a) is carried out in toluene or heptane.

14. The process according to claim 1 , wherein step (a) is carried out in the presence of ethylene glycol.

15. The process according to claim 1 , wherein step (c) is carried out in the presence of citric acid.

16. The process according to claim 1 , wherein the weight ratio of the cis-diastereomers to the trans-diastereomers of the mixture of compounds of formula (I) is less than 40:60.

17. The process according to claim 1 , wherein the weight ratio of the cis-diastereomers to the trans-diastereomers of the prepared mixture after separating the trans-diastereomers and cis-diastereomers is at least 60:40.

18. The process according to claim 1 , wherein the ketal formation comprises formation of a ketal compound according to formula

wherein R 1 represents a C 1-8 alkyl group, a C 2-8 alkenyl group or a C 2-8 alkynyl group, each optionally substituted with one or two of a C 1-4 alkyl alkoxy ether group and/or C 1-4 alkyl carboxylester group, and R 2 represents a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 2-6 alkynyl group, each optionally substituted with an C 1-4 alkyl alkoxy ether group, a carboxylic acid group or a C 1-4 alkyl carboxylester group, and
R 3 represent, each independently, a C 2-3 alkyl group or, when two R 3 taken together, is a bivalent group —C(R 4 )H—(C(R 4 ) 2 ) n —H(R 4 )C— wherein n is an integer from 0 to 3 and R 4 , each independently, is a hydrogen or C 1-3 alkyl group, with the proviso that at least one R 4 is a linear or branched C 1-3 alkyl group when n is 0.

Assignees

• Firmenich & Cie

Inventors

• Jacoby Denis
• Bonomo Lucia

Classifications

• C07C2601/08

  the ring being saturated · CPC title

• C07C67/327 Primary

  by elimination of functional groups containing oxygen only in singly bound form · CPC title

• C07C69/716

  Esters of keto-carboxylic acids {or aldehydo-carboxylic acids} · CPC title

• C07C69/708

  Ethers · CPC title

• C07C67/313

  by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups · CPC title