Process for the preparation of the lactone of 1R, cis 2,2-dimethyl-3-formyl-cyclopropane-1-carboxylic acid

• US 5,276,167 A
• Filed: 10/21/1992
• Issued: 01/04/1994
• Est. Priority Date: 11/08/1991
• Status: Expired due to Term

• Current Assignee: Hoechst Marion Rousse
• Original Assignee: Roussel Uclaf
• Inventors: Bhatnagar, Neerja, Brion, Francois, Colladant, Colette
• Primary Examiner(s): Ivy, C. Warren
• Assistant Examiner(s): COVINGTON, RAYMOND K
• Application Number:
  US07/964,500
• Time in Patent Office: 440 Days
• Field of Search: 549/313, 549/302
• US Class Current: 549/302
• CPC Class Codes: C07D 307/93 condensed with a ring other than six-membered

Abstract

A process for preparation of a compound of the formula ##STR1##

Claims

1. A process for preparation of a compound of the formula ##STR10## comprising reacting a compound of the formula ##STR11## of 1R,cis configuration with at least 2 equivalents of a halogen selected from the group consisting of chlorine, bromine and iodine to obtain either a compound of the formula ##STR12## or a compound of the formula ##STR13## or a compound of the formula ##STR14## in which X is halogen as defined above optionally in a mixture with a compound of the formula ##STR15## optionally continuing the halogenation of the compound of formula III₁ or III₂ with excess halogen as defined above to obtain the compound of formula III₃, reacting the compound of formula III₃ optionally in the form of a mixture with a compound of formula IV with a basic agent to obtain the compound of formula IV, existing in that case in the reaction medium in the form of its salt corresponding to the basic agent used, or of that of the open form ##STR16## optionally acidifying the reaction medium to obtain the acid of formula IV or IV'"'"' and reacting the said acid or the said salt with an oxidizing agent to obtain the compound of formula I.

2. The process of claim 1 wherein the compound of formula II of 1R,cis configuration is reacted with at least 4 equivalents of halogen to obtain the compound of formula III₃, in a mixture with a compound of formula IV, then reacting said mixture as indicated in claim 1 to obtain the compound of formula I.

3. The process of claim 1 wherein the halogen is chlorine or bromine.

4. The process of claim 1 wherein the reaction is effected in a halogenated organic solvent or an organic ester.

5. The process of claim 1 wherein the crude reaction medium of the halogenation is treated with a basic agent selected from the group consisting of alkali metal and alkaline earth metal hydroxides and carbonates before isolating the halogenated compound.

6. The process of claim 1 wherein the basic agent is selected from the group consisting of alkali metal, alkaline earth metal and magnesium hydroxides and carbonates in the presence of water.

7. The process of claim 1 wherein the oxidizing agent is selected from the group consisting of hypohalogenous acids, alkali metal, alkaline earth metal and magnesium hypohalites, potassium permanganate, chromic anhydride, periodic acid and the alkali metal bismuthates.

8. The process of claim 1 wherein the oxidizing agent is a hypohalogenous acid.

9. The process of claim 8 wherein the hypohalogenous acid is obtained in situ from an alkali metal, alkaline earth metal or magnesium hypohalite in acid medium.

10. The process of claim 9 wherein the oxidizing agent is hypochlorous acid.

11. The process of claim 9 wherein the hypochlorous acid is obtained in situ from sodium hypochlorite placed in acid medium.

12. The process of claim 9 wherein the acid is selected from the group consisting of lower alkanoic acids and solutions of phosphates, borates and acetates of appropriate pH.

13. The process of claim 12 wherein the acid is acetic acid or propionic acid.

14. A compound selected from the group consisting of formula ##STR17## wherein X is halogen.