Process for the stereoselective preparation of a pyrazole carboxamide

Patent metadata

Field	Value
Publication number	US-9120759-B2
Application number	US-201314373439-A
Country	US
Kind code	B2
Filing date	Feb 13, 2013
Priority date	Feb 15, 2012
Publication date	Sep 1, 2015
Grant date	Sep 1, 2015

Abstract

The present invention relates to a process for the enantioselective preparation of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid ((1S,4R)-9-dichloromethylene-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl)-amide of formula Ib.

First claim

What is claimed is:

1. A process for the enantioselective preparation of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid ((1S,4R)-9-dichloromethylene-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl)-amide of formula lb

which process comprises
a) reducing a compound of formula II

with an enantioselective reagent to a compound of formula IIIe

b) dehydrating the compound of formula IIIe in the presence of an acid to the compound of formula IVa

c) reacting the compound of formula IVa with hydroxylamine to the compound of formula Va

and
d) acylating the oxime oxygen of the compound of formula Va in the presence of a solvent and an acylating agent and finally reacting the obtained product with the compound of formula VI

 or
e) reacting the compound of formula V with an excess of the compound of formula VI.

2. A process according to claim 1 , wherein the enantioselective reduction of the compound of formula II is done via hydrogenation in the presence of a transition metal catalyst.

3. A process according to claim 1 , wherein the enantioselective reduction of the compound of formula II is done via transfer hydrogenation in the presence of a transition metal catalyst.

4. A process according to claim 1 , wherein the enantioselective reagent is a ruthenium catalyst.

5. A process according to claim 2 , wherein the enantioselective reagent is a ruthenium catalyst.

6. A process according to claim 3 , wherein the enantioselective reagent is a ruthenium catalyst.

7. A process according to claim 1 , wherein the enantioselective reagent is chloro{(R)-(+)-2,2′-bis[di(3,5-xylyl)phosphino]-1,1′-binaphthyl}[(2R)-(+)1-(4-methoxyphenyl) -1′-(4-methoxyphenyl-kC)-3-methyl-1,2-butanediamine]ruthenium(II).

8. A process according to claim 1 , wherein the enantioselective reagent is dichloro[(4S,5S)-(+)-4,5-bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxolane ][(S)-(−)-2-(α-methylmethanamine)-1 H-benzimidazole]ruthenium(II).

9. The compound (1S,4R)-9-dichloromethylene-8-hydroxy -octahydro-1,4-methano-naphthalen-5-one of formula IIle

or a spatial isomer thereof.

10. The compound (1S,4R)-9-dichloromethylene-2,3,4,6,7,8-hexahydro-1 H-1 ,4-methano-naphthalen-5-one of formula

or a spatial isomer thereof.

11. The compound (1 S,4R)-9-dichloromethylene-2,3,4,6,7,8-hexahydro-1H-1,4-methano-naphthalen-5-one oxime of formula Va

or a spatial isomer thereof.

12. A compound of formula XXIIIa

wherein X is oxygen or sulfur, R 1 is C 1 -C 6 alkoxy, CH 3 —C(═CH 2 )—O —, phenoxy or trichloromethoxy; or a spatial isomer thereof.

13. A compound of formula XXIVa

wherein X is oxygen or sulfur, or a spatial isomer thereof.

Assignees

• Syngenta Participations Ag

Inventors

• Smejkal Tomas

Classifications

• C07C2603/66

  containing five-membered rings · CPC title

• C07C251/66

  with the esterifying carboxyl groups bound to hydrogen atoms, to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings · CPC title

• C07C49/693

  polycyclic · CPC title

• C07C251/62

  having oxygen atoms of oxyimino groups esterified · CPC title

• C07D231/14 Primary

  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 · CPC title