Process for the preparation of substituted carboxylic esters

1. A process for the preparation of 2(S)-alkyl-5-halogenpent-4-ene carboxylic esters by enzymatic hydrolysis, comprising the steps

a) enzymatic hydrolysis of racemic 2-alkyl-5-halogenpent-4-ene carboxylic esters in aqueous and alkaline medium in the presence of an esterase;

b) isolation of 2(S)-alkyl-5-halogenpent-4-ene carboxylic esters by extraction with an organic solvent;

c) isolation of 2(R)-alkyl-5-halogenpent-4-ene carboxylic acids from the aqueous-alkaline medium;

d) esterification of 2(R)-alkyl-5-halogenpent-4-ene carboxylic acids to 2(R)-alkyl-5-halogenpent-4-ene carboxylic esters,

e) subsequent racemization to form 2-alkyl-5-halogenpent-4-ene carboxylic esters; and

f) return of the racemate obtained in step e) to step a), if necessary together with fresh racemic 2-alkyl-5-halogenpent-4-ene carboxylic esters.

2. The process according to claim 1 , wherein 2(S)-alkyl-5-halogenpent-4-ene carboxylic ester corresponds to formula I,

wherein

R is an organic group with 1 to 18 C-atoms, R 1 is C 1 –C 6 alkyl, Z is chlorine, bromine or iodine, and the OR group forms an ester group with the carbonyl residue.

3. The process according to claim 1 , wherein the racemate used in process a) corresponds to formula II.

wherein

R is an organic group with 1 to 18 C-atoms, R 1 is C 1 –C 6 alkyl, Z is chlorine, bromine or iodine, and the OR group forms an ester group with the carbonyl residue.

4. The process according to claim 1 , wherein 2(R)-alkyl-5-halogenpent-4-ene carboxylic acid corresponds to formula III,

wherein R 1 is C 1 –C 6 alkyl and Z is chlorine, bromine or iodine.

5. The process according to claim 2 , wherein Z is chlorine.

6. The process according to claim 2 , wherein R is C 1 –C 18 alkyl.

7. The process according to claim 6 , wherein the alkyl is methyl or ethyl.

8. The process according to claims 2 , wherein R 1 is C 1 –C 4 alkyl, and Z is chlorine.

9. The process according to claims 2 , wherein Z is chlorine, R 1 is i-propyl, and R is methyl or ethyl.

10. The process according to claim 1 , wherein the enzymatic hydrolysis in process step a) is performed with diluted, aqueous KOH or NaOH.

11. The process according to claim 1 , wherein the isolation is performed by means of extraction with an organic solvent which is not miscible with water.

12. The process according to claim 1 , wherein the 2(R)-alkyl-5-halogenpent-4-ene carboxylic acids are isolated by extraction with an organic solvent, the reaction mixture being acidified beforehand.

13. The process according to claim 1 , wherein the 2(R)-alkyl-5-halogenpent-4-ene carboxylic acid is either esterified with an esterification agent, or the carboxylic acid is converted to the acyl halide before esterification.

14. The process according to claim 1 , wherein the racemization following the esterification after process step d) is performed in the same reaction vessel without isolation of the 2(R)-alkyl-5-halogenpent-4-ene carboxylic ester.

15. The process according to claim 1 , wherein the racemization is performed in the presence of an alkali metal alcoholate at elevated temperatures.

16. The process according to claim 3 , wherein Z is chlorine.

17. The process according to claim 4 , wherein Z is chlorine.

18. The process according to claim 3 , wherein R is C 1 –C 18 alkyl.

19. The process according to claim 18 , wherein the alkyl is methyl or ethyl.

20. The process according to claim 3 , wherein R 1 is C 1 –C 4 alkyl, and Z is chlorine.

21. The process according to claim 4 , wherein R 1 is C 1 –C 4 alkyl, and Z is chlorine.

22. The process according to claim 3 , wherein Z is chlorine, R 1 is i-propyl, and R is methyl or ethyl.

23. The process according to claim 4 , wherein Z is chlorine, R 1 is i-propyl, and R is methyl or ethyl.