Process for preparing alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrates

• US 20110004002A1
• Filed: 02/27/2009
• Published: 01/06/2011
• Est. Priority Date: 02/29/2008
• Status: Active Grant

• Current Assignee: BASF SE
• Original Assignee: BASF SE
• Inventors: Smidt, Sebastian Peer, Koradin, Christopher, Keil, Michael, Zierke, Thomas, Wolf, Bernd, Rack, Michael, Maywald, Volker
• Granted Patent: US 8,207,354 B2
• Time in Patent Office: Days
• US Class Current: 548/374.1
• CPC Class Codes: C07C 67/343 by increase in the number of carbon atoms
• CPC Class Codes: C07C 69/72 Acetoacetic acid esters
• CPC Class Codes: C07D 231/14 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

Abstract

A process for preparing alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrates (VI)

where R is methyl or ethyl,
from crude reaction mixtures of alkyl 4,4-difluoroacetoacetates (I)

by

• a) reacting

• • where M is a sodium or potassium ion, and

• • without additional solvent to form an enolate (V)

• b) releasing the corresponding alkyl 4,4-difluoroacetoacetate (I) from the enolate (V) by means of acid,
• c) removing the salt formed from cation M and acid anion as a solid and
• d) converting (I), without isolation from the crude reaction mixture, to the alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrate (VI),
  and the use of (VI) for preparing 1-methyl-3-difluoromethyl-pyrazol-3-ylcarboxyates VII

Claims

1-10. -10. (canceled)

11. A process for preparing an alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrate of the formula (VI)

12. The process according to claim 11, wherein process stage a) is carried out by initially charging alkyl acetate (II) and alkyl difluoroacetate (IV) and metering the alkoxide (III) in.

13. The process according to claim 11, wherein (I) is released from (V) with exclusion of water or in the presence of a small water content.

14. The process according to claim 11, wherein the acid used for the release of (I) from (V) in process stage b) is hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, formic acid, acetic acid, oxalic acid, citric acid, methanesulfonic acid, or p-toluenesulfonic acid.

15. The process according to claim 11, wherein the release of (I) from (V) in process stage b) is carried out in the presence of a small water content.

16. The process according to claim 11, wherein the molar ratio of alkyl acetate (II) to alkoxide (III) is from 0.8:

1 to 10;

1.

17. The process according to claim 11, wherein the molar ratio of alkyl difluoroacetate (IV) to alkyl acetate (II) is from 1:

0.8 to 1;

20.

18. The process according to claim 11, wherein the molar ratio of alkoxide (III) to acid is from 1:

0.7 to 1;

5.

19. The process according to claim 11, wherein the reaction temperature for the reaction of (II), (III) and (IV) is from −

20°

C. up to 70°

C.

20. A method of preparing a 1-methyl-3-difluoromethyl-pyrazol-3-ylcarboxyate of the formula VII

21. The method of claim 20, wherein said cyclizing comprises reacting the compound of formula VI with methylhydrazine.