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

Patent metadata

Field	Value
Publication number	US-9758500-B2
Application number	US-201615291129-A
Country	US
Kind code	B2
Filing date	Oct 12, 2016
Priority date	Apr 16, 2012
Publication date	Sep 12, 2017
Grant date	Sep 12, 2017

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

The invention claimed is:

1. A process for preparing compounds of formula I

in which
R 1 is a straight-chain or branched, optionally mono- or polyunsaturated hydrocarbyl radical, and R 2 is H or C 1 -C 6 -alkyl, where
a) a carbonyl compound of formula II

in which R 1 and R 2 have the meanings above, is reacted by means of Wittig olefination to give a cyclopropane of formula (III)

b) the cyclopropane of the formula III is reacted, with ring opening, to give a compound of formula IV

in which X is halogen or O—R′, in which R′ is H, acyl, Tf-acetyl or SO 2 —R″, and R″ is alkyl or aryl; and
c) the compound of the formula IV is converted to the formula I compound.

2. The process according to claim 1 , where a cyclopropylphosphonium salt is used for the Wittig olefination according to stage a).

3. The process according to claim 2 , in which the cyclopropylphosphonium salt is a triphenylphosphonium compound of formula V

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

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

5. The process according to claim 1 , wherein the ring-opening in stage b) takes place in the presence of a Lewis acid or Brönstedt acid/protonic acid, and a nucleophile.

6. The process according to claim 5 , where the ring opening of step b) provides E-selectively with respect to R 1 , where E:Z is greater than 1.5.

7. The process according to claim 1 , wherein for stage c), X is OR′, and carrying out an ester cleavage, or X is halogen, and converting the halide to a corresponding ester, and then cleaving the corresponding ester.

8. The process according to claim 1 , wherein the formula I compound is (3E,7E)-homofarnesol of formula Ia

9. The process according to claim 8 , where, in stage a), E-geranyl acetone of formula IIa

is reacted with cyclopropylphosphonium halogenide to provide a compound of formula IIIa

10. A process for preparing enantiomerically pure ambrox or a stereoisomer mixture of ambrox, where (3E,7E)-homofarnesol is prepared by a process according to claim 1 and the (3E,7E)-homofarnesol is cyclized to give enantiomerically pure (−)-ambrox, 3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan, or a stereoisomer mixture of 3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan.

11. The process according to claim 6 , where the E-selectivity with respect to R 1 is a molar excess of E:Z in a range from 2:1 to 50:1.

12. The process according to claim 1 , where R 1 is a C 1 -C 20 hydrocarbyl radical with one or more conjugated or non-conjugated double bond.

13. The process according to claim 12 , where R 2 is a methyl or ethyl.

14. The process according to claim 1 , where R 2 is a methyl or ethyl.

15. The process according to claim 14 , where R 1 is a C 1 -C 20 hydrocarbyl radical with one or more non-conjugated radicals of formula

where n is 2, 3, or 4.

Assignees

• Basf Se

Inventors

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

Classifications

• C07C13/04

  with a three-membered ring · CPC title

• C07C29/124

  of halides · CPC title

• C07D307/92 Primary

  Naphthofurans; Hydrogenated naphthofurans · CPC title

• C07C29/58

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

• C07C2601/02

  with a three-membered ring · CPC title