Patent EA-003364-B1 (EA)
Title: Method for preparing vitamin a
Inventor: ANCEL JEAN-ERICK
IPC: C07C47/11
Filed: 1999-07-07
Abstract: 1. A method for preparing an intermediate of vitamin A of formula: wherein, in a first step, ethynyl-retro-alpha-ionol is acetylated, in a second step, the ethynyl-retro-alpha-ionol acetate is isomerized to allene acetate and, in a final step, the compound obtained in the second step is hydrolyzed. 2. The method as claimed in claim 1, wherein the first step is carried out by bringing ethynyl-retro-alpha-ionol into contact with acetic anhydride or acetyl chloride in the presence of a tertiary amine. 3. The method as claimed in claim 2, wherein the tertiary amine is triethylamine, trimethylamine, tributylamine or pyridine. 4. The method as claimed in claim 2, wherein an activating agent such as dimethylamino pyridine is added. 5. The method as claimed in claim 2, wherein an inert solvent chosen from optionally halogenated aromatic or aliphatic solvents is used. 6. The method as claimed in claim 1, wherein the second step is carried out in the presence of a copper-based metal catalyst. 7. The method as claimed in claim 6, wherein copper chloride is used. 8. The method as claimed in claim 6 and 7, wherein a molar ratio of copper salt to ethynyl-retro-alpha-ionol acetate of between 0.5% and 5% is used. 9. The method as claimed in claim 6, wherein the reaction solvent is chosen from the optionally halogenated aromatic or aliphatic solvents and esters. 10. The method as claimed in claim 9, wherein the solvent is monochlorobenzene. 11. The method as claimed in claim 6, wherein the concentration of propargyl acetate in the reaction solvent is between 0.1 and 1 mol per liter, preferably about 0.5 mol per liter. 12. The method as claimed in claim 6, wherein the temperature used does not cause degradation of the propargyl acetate. 13. The method as claimed in claim 12, wherein the temperature is between 100 and 150 degree C. 14. An allene acetate of formula: 15. The method as claimed in claim 1, wherein the third step is carried out in the presence of an acid in a ketone solvent or in an aromatic solvent, optionally halogenated. 16. The method as claimed in claim 15, wherein the isomerization and deacetylation catalyst is an inorganic acid chosen from hydrochloric acid, hydrobromic acid or sulfuric acid. 17. The method as claimed in claim 15 and 16, wherein the reaction is carried out in the presence of hydrobromic acid in acetone. 18. Use of an intermediate as claimed in claim 14 for preparing vitamin A. 19. A method for preparing vitamin A, wherein in a first step beta-ionbne is isomerized to retro-alpha-ionone in the presence of a strong base chosen from alkali metal alcoholates or alkali metal hydroxides in a polar aprotic solvent, in a second step ethynylation of the compound obtained in the first step is carried out in the presence of magnesium or lithium acetylide, in a third step acetylation is carried out under conditions defined in claims 2 to 6, in a fourth step the compound obtained in step three is condensed with an ether or an ester of methylbutadiene in the presence of a Lewis acid and in a fifth step the compound obtained in step four is isomerized in the presence of an inorganic acid, such as hydrochloric acid, hydrobromic acid or sulfuric acid. 20. The method as claimed in claim 19, wherein in the first step, the base is chosen from alkali metal alcoholates and alkali metal hydroxides. 21. The method as claimed in claim 19 and 20, wherein the molar ratio between the base and the beta-ionone is between 1 and 1.5. 22. The method as claimed in claims 19 to 21, wherein the solvent is chosen from dimethyl sulfoxide, N-methylpyrrolidone or dimethylformamide. 23. The method as claimed in claim 19, wherein in the second step, the magnesium acetylide is formed in situ by mixing acetylene and isopropylmagnesium chloride. 24. The method as claimed in claim 19 and 23, wherein the solvent used is chosen from ethers and polar solvents, such as aromatic solvents. 25. The method as claimed in claim 19, wherein the ether or the ester of methylbutadiene used in step 4 is a 3-methoxy-1-methylbutadiene, 3-trimethylsilyloxy-1-methylbutadiene. 26. The method as claimed in claim 19 and 25, wherein the condensation in step 4 is carried out in the presence of a Lewis acid chosen from zinc chloride, titanium tetrachloride, boron trifluoride, or trityl salts. 27. The method as claimed in claims 19 and 26, wherein a polar solvent chosen from nitroalkanes and chlorinated solvents is used. 28. The method as claimed in claim 19, wherein the fifth step is carried out in the presence of an inorganic acid chosen from hydrochloric acid, hydrobromic acid or sulfuric acid.