Preparation of 1,3-diphenylprop-2-en-1-one derivatives

• US 20060142611A1
• Filed: 07/08/2004
• Published: 06/29/2006
• Est. Priority Date: 07/08/2003
• Status: Active Grant

• Current Assignee: Genfit SA
• Original Assignee: Genfit SA
• Inventors: Delhomel, Jean-Francois, Caumont-Bertrand, Karine
• Granted Patent: US 7,385,082 B2
• Time in Patent Office: Days
• US Class Current: 560/51
• CPC Class Codes: C07C 319/20 by reactions not involving the formation of sulfide groups
• CPC Class Codes: C07C 323/22 containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
• CPC Class Codes: C07C 51/09 from carboxylic acid esters or lactones
• CPC Class Codes: C07C 59/90 containing singly bound oxygen-containing groups
• CPC Class Codes: C07C 67/31 by introduction of functional groups containing oxygen only in singly bound form
• CPC Class Codes: C07C 69/712 the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The invention relates to a method for the preparation of de 1,3-diphenylprop-2-en-1-one substituted on one of the two phenyl groups by a carboxyalkyloxy group or a carboxyalkylthio group.

Claims

1-13. -13. (canceled)

14. A method for preparing 1,3-diphenylprop-2-en-1-one derivatives substituted by a carboxyalkyloxy or carboxyalkylthio group, comprising the following steps:

(i) contacting at least one 1,3-diphenylprop-2-en-1-one derivative substituted on one of the two phenyl groups by a hydroxyl or thiol group with at least one halogenated compound represented by general formula (II);

in which Y represents a halogen atom, R is a C1-C24 alkyl chain and R′

is an acid-labile protective group of carboxylic acid;

(ii) acid hydrolysis of the ester obtained in step (i).

15. The method according to claim 14, wherein the carboxylic acid protective group of the compound represented by formula (II) is selected from acid-labile groups of the C1 to C5 alkyl type substituted at the carbon atom linked to the carboxylic function by one or two linear or branched alkyl groups containing from 1 to 4 carbon atoms.

16. The method according to claim 14, wherein the carboxylic acid protective group of the compound represented by formula (II) is selected from tert-butyl and isopropyl groups.

17. The method according to claim 14, wherein R is a C1-C10 alkyl chain, optionally substituted by one or more hydrocarbon groups, saturated, linear or cyclic containing from 1 to 12 carbon atoms.

18. The method according to claim 14, wherein step (i) is carried out at a temperature comprised between 25 and 120°

C. and more preferably between 80 and 120°

C.

19. The method according to claim 14, wherein step (i) is carried out in the presence of a catalyst.

20. The method according to claim 14, wherein step (i) is carried out in the presence of cesium or potassium carbonate as catalyst.

21. The method according to claim 14, wherein step (i) is repeated by several additions of the halogenated compound represented by general formula (II) and if necessary of the catalyst.

22. The method according to claim 14, wherein 1,3-diphenylprop-2-en-1-one derivative substituted by a hydroxyl or thiol group, which is used in step (i) is obtained by a Claisen-Schmidt reaction in acidic or basic medium of a compound of the type acetophenone with a thio- or hydroxy-benzaldehyde derivative, or of a thio- or hydroxy-acetophenone derivative with a compound of the benzaldehyde type.

23. The method according to claim 14, wherein acid hydrolysis step (ii) is carried out by contacting a 1,3-diphenylprop-2-en-1-one derivative substituted by an alkyloxycarbonylalkyloxy or alkyloxycarbonylalkylthio group with trifluoroacetic acid.

24. The method according to claim 14, wherein acid hydrolysis step (ii) is carried out by contacting a 1,3-diphenylprop-2-en-1-one derivative substituted by an alkyloxycarbonylalkyloxy or alkyloxycarbonylalkylthio group with trifluoroacetic acid in an amount from 1 to 20 equivalents, and preferably from 8 to 12 equivalents.

25. The method according to claim 14, wherein step (ii) is carried out at a temperature of 0 to 100°

C. and more preferably 18 to 25°

C.

26. The method according to claim 14, wherein the product so prepared is represented by the following general formula: