Process for the preparation of (3e, 7e)-homofarnesol

Patent metadata

Field	Value
Publication number	US-2016200648-A1
Application number	US-201514804747-A
Country	US
Kind code	A1
Filing date	Jul 21, 2015
Priority date	Apr 16, 2012
Publication date	Jul 14, 2016
Grant date	—

Abstract

The present invention relates to new types of processes for the improved preparation of homofarnesol, in particular of (3E,7E)-homofarnesol and homofarnesol preparations with an increased content of (3E,7E)-homofarnesol (also referred to as all E-homofarnesol).

First claim

1 .- 12 . (canceled)

13 . A process for preparing (3E,7E)-homofarnesol of formula Ia

which comprises
a) reacting a carbonyl compound of the formula II

in which R 1 is

where the dotted line represents a bond to the carbonyl carbon of formula II, and R 2 is methyl,
by means of Wittig olefination to give a cyclopropane of the general formula (III)

in which R 1 and R 2 have the meanings given above,

b) reacting the cyclopropane of the formula III with ring opening in the presence of a Lewis acid or a Brönstedt acid/protonic acid, and a nucleophile, to give a compound of the formula IV

in which R 1 and R 2 have the meanings given above, and X is halogen or O—R′, in which R′ is acyl, Tf-acetyl or SO 2 —R″, in which R″ is alkyl or aryl, wherein the ring opening exhibits E-selectively, with respect to R 1 , with a E:Z ratio of greater than 2:1; and

c) converting the compound of the general formula IV to the compound of the general formula I by, when X is OR′, carrying out an ester cleavage, or when X is halogen, converting the halide to an ester and then cleaving this ester.

14 . The process according to claim 13 , wherein a cyclopropylphosphonium salt is used for the Wittig olefination according to stage a).

15 . The process according to claim 14 , wherein the cyclopropylphosphonium salt is a triphenylphosphonium compound of the formula V

in which Z − is the anion of a strong acid.

16 . The process according to claim 15 , wherein Z is a halide.

17 . The process according to claim 15 , wherein Z is bromide.

18 . The process according to claim 15 , wherein the compound of the formula V is prepared by reacting a) bromobutyrolactone with triphenylphosphine and then thermally decarboxylating the reaction product, or b) reacting 1,3-dibromopropane with triphenylphosphine and then cyclizing the reaction product.

19 . The process according to claim 13 , wherein, in stage c), the compound of the general formula IV is converted to a compound of the general formula I by, when X is OR′, carrying out an ester cleavage, or when X is halogen, converting the halide to an ester and then cleaving this ester.

20 . The process according to claim 13 , wherein, in stage c), the compound of the general formula IV is converted to a compound of the general formula I by, when X is OR′, carrying out an ester cleavage, or when X is halogen, converting the halide to a formate ester, and then cleaving this ester.

21 . The process according to claim 13 , in which a product comprising a (3E,7E)-homofarnesol of the formula Ia

is obtained.

22 . The process according to claim 13 , where, in stage a), E-geranyl acetone of the formula IIa

is reacted with cyclopropylphosphonium halogenide, so that the cyclopropane of the formula IIIa

is obtained.

23 . A compound of the formula IIIa

24 . A process for preparing enantiomerically pure ambrox or a stereoisomer mixture of ambrox, the process comprising;
preparing (3E,7E)-homofarnesol by the process according to claim 13 , and conducting a cyclization reaction of the (3E,7E)-homofarnesol chemically or enzymatically to give enantiomerically pure ambrox or a stereoisomer mixture of ambrox.

Assignees

• Basf Se

Inventors

• Bonnekessel-Weingarten Melanie
• Ernst Hansgeorg
• Siegel Wolfgang
• Winterfeldt Ekkehard
• Hoffmann Reinhard W

Classifications

• C07C2601/02

  with a three-membered ring · CPC title

• C07C29/58

  by elimination of halogen, e.g. by hydrogenolysis, splitting-off (C07C29/124 takes precedence) · CPC title

• C07D307/92 Primary

  Naphthofurans; Hydrogenated naphthofurans · CPC title

• C07C29/38 Primary

  by reaction with aldehydes or ketones · CPC title

• C07C29/124

  of halides · CPC title