Process for the production of 9-(Z)-retinoic acid

1. A process for the preparation of 9-(Z)-retinoic acid, comprising reacting an alkali metal salt of 3-methyl-4-oxocrotonic acid of the formula

wherein M stands for sodium or potassium, with the (Z)-isomer of a C 15 -triphenyl phosphonium salt of the formula

wherein X stands for a halogen, in the presence of a base.

2. The process according to claim 1 , wherein the alkali metal salt of methyl-4-oxocrotonic acid is prepared in situ from an alkyl-3-methyl-4-oxocrotonate which is hydrolyzed in the presence of an alkali hydroxide.

3. The process according to claim 2 , wherein M stands for potassium, and the potassium salt of methyl-4-oxocrotonic acid is prepared in situ from ethyl-3-methyl-4-oxocrotonate which is hydrolyzed in the presence of potassium hydroxide.

4. The process according to claim 1 , wherein X − in formula II is chlorine.

5. The process according to claim 1 , wherein the (Z)-isomer of a C 15 -triphenyl phosphonium salt is isolated from an isomeric mixture of the (Z)-isomer and the (E)-isomer, comprising the steps:

a) extracting a concentrate of the isomeric mixture with methylene chloride,

b) taking up the organic phase in ethylacetate/n-butanol,

c) distilling off ethylacetate/methylene chloride,

d) replacing the distilled amount with ethylactetate, and

e) crystallizing out the (Z)-isomer.

6. The process according to claim 1 , wherein the reaction is performed at a temperature of from −15° C. to 15° C.

7. The process according to claim 1 , wherein the reaction is performed in the presence of a lower alcohol.

8. The process according to claim 1 , wherein the base is an alkali hydroxide.

9. The process according to claim 8 , wherein the base is potassium hydroxide.

10. The process according to claim 1 , wherein the process further comprises:

a) extracting the alkali metal salt of 3-methyl-4-oxocrotonic acid and (Z)-isomer of a C 15 -triphenyl phosphonium salt mixture with methylene chloride,

b) setting the pH of the water phase to about 3 to 4 with a mineral acid,

c) extracting with methylene chloride,

d) exchanging solvent with methanol by distilling off methylene chloride and introducing methanol, and

e) isolating the 9-(Z)-retinoic acid which crystallizes from the mixture.

11. The process according to claim 5 , wherein the isomeric mixture is comprised in a mother liquor obtained from the preparation of β-carotene, and the ratio of the (Z) to the (E) isomer in the mixture is about 2:1.

12. The process according to claim 1 , wherein the reaction temperature is from −15° C. to 15° C.

13. The process according to claim 1 , wherein the reaction occurs substantially free from the presence of light and oxygen.