Process for the stereoselective preparation of a pyrazole carboxamide

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.