Process for the preparation of optically active isoxazoline compounds

Patent metadata

Field	Value
Publication number	US-9815829-B2
Application number	US-201515501008-A
Country	US
Kind code	B2
Filing date	Aug 4, 2015
Priority date	Aug 11, 2014
Publication date	Nov 14, 2017
Grant date	Nov 14, 2017

Abstract

The present invention relates to a process for the preparation of a compound of formula (I) wherein A 1 and A 2 are C—H, or one of A 1 and A 2 is C—H and the other is N; R 1 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 3 -C 6 cycloalkyl; each R 2 is independently bromo, chloro, fluoro or trifluoromethyl; R 3 is hydrogen; R 4 is hydrogen, halogen, methyl, halomethyl or cyano; or R 3 and R 4 together form a bridging 1,3-butadiene group; R 5 is chlorodifluoromethyl or trifluoromethyl; n is 2 or 3; by reacting a compound of formula (II) wherein A 1 , A 2 , R 1 , R 2 , R 3 , R 4 , R 5 and n is as defined under formula (I) above, with hydroxylamine, a base and a chiral catalyst, characterized in that the chiral catalyst is a dimeric chiral catalyst of formula (III) wherein R 6 , R 7 , R 8 , R 9 , R 10 and X are as defined in claim 1 .

First claim

The invention claimed is:

1. A process for the preparation of a compound of formula I

wherein
A 1 and A 2 are C—H, or one of A 1 and A 2 is C—H and the other is N;
R 1 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 3 -C 6 cycloalkyl;
each R 2 is independently bromo, chloro, fluoro or trifluoromethyl;
R 3 is hydrogen;
R 4 is hydrogen, halogen, methyl, halomethyl or cyano;
or R 3 and R 4 together form a bridging 1,3-butadiene group;
R 5 is chlorodifluoromethyl or trifluoromethyl;
n is 2 or 3;
by reacting a compound of formula II

wherein
A 1 , A 2 , R 1 , R 2 , R 3 , R 4 , R 5 and n is as defined under formula I above, with hydroxylamine, a base and a chiral catalyst, characterized in that the chiral catalyst is a dimeric chiral catalyst of formula III

wherein
each R 6 is ethyl or vinyl;
R 7 , R 8 , R 9 and R 10 are halogen, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl; and
X is a halogen anion or BF 4 —, PF 6 − , HSO 4 — or an C 1 -C 3 alkylsulfonate, benzenesulfonate or methyl-benzenesulfonate.

2. A process according to claim 1 , wherein in the catalyst of formula III
each R 6 is vinyl;
each of the substituents R 7 , R 8 , R 9 and R 10 has the same meaning and represent halogen and X is chloride or bromide or BF 4 — or PF 6 − .

3. A process according to claim 1 , wherein in the catalyst of formula III
each R 6 is vinyl;
each of the substituents R 7 , R 8 , R 9 and R 10 has the same meaning and represent fluoro or chloro; and
X is chloride or bromide.

4. A process according to claim 1 , wherein the amount of hydroxylamine is from 1 to 10 equivalents.

5. A process according to claim 1 , wherein the amount of base is from 0.05 to 2 equivalents.

6. A process according to claim 1 , wherein the amount of catalyst is from 0.01 to 0.4 equivalents.

7. A compound of formula III

wherein
each R 6 is ethyl or vinyl;
R 7 , R 8 , R 9 and R 10 are halogen, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl;
and X is a halogen anion, BF 4 —, PF 6 − or an C 1 -C 3 alkylsulfonate, benzenesulfonate or methyl-benzenesulfonate.

8. A compound of formula III according to claim 7 , wherein
each R 6 is vinyl;
each of the substituents R 7 , R 8 , R 9 and R 10 has the same meaning and represent halogen; and
X is chloride, bromide or BF 4 —.

9. A compound of formula Ill according to claim 7 , wherein
each R 6 is vinyl;
each of the substituents R 7 , R 8 , R 9 and R 10 has the same meaning and represent fluoro or chloro; and
X is chloride or bromide.

Assignees

• Syngenta Participations Ag

Inventors

• Smejkal Tomas
• Smits Helmars

Classifications

• C07D261/14

  Nitrogen atoms · CPC title

• B01J2231/324

  Cyclisations via conversion of C-C multiple to single or less multiple bonds, e.g. cycloadditions · CPC title

• B01J31/0244

  with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine · CPC title

• C07D453/04 Primary

  having a quinolyl-4, a substituted quinolyl-4 or a alkylenedioxy-quinolyl-4 radical linked through only one carbon atom, attached in position 2, e.g. quinine · CPC title

• B01J31/02

  containing organic compounds or metal hydrides · CPC title