Enantioselective process for the manufacture of lactam carboxylate derivatives

An enantioselective process for the manufacture of a compound of formula (D)

• wherein ring A is a di-substituted pyrazole, substituted on a ring nitrogen by RB2 and substituted on a ring carbon by RB3, wherein RB2 is C1-C3 alkyl or C1-C3fluoroalkyl and each RB3 is halogen, C1-C3fluoroalkyl, C1-C3haloalkoxy, C1-C3alkoxy, C1-C3haloalkyl, C1-C3fluoroalkyl, C1-C3haloalkoxy, C1-C3alkoxy, or C1-C3alkyl, said enantioselective process comprising:
• (i) reacting a halogenated pyrazole of formula (A),
• wherein Hal is halogen selected from iodo, bromo and chloro;
• with isopropylmagnesium chloride-lithium chloride in a suitable solvent and subsequently adding 1-dimethylamino-2-nitroethylene to give a compound of formula (B)
• (ii) reacting the compound of formula (B) from step (i) with a malonate in solvent, under enantioselective nickel catalysis to give the compound of formula (C)
• and
• (iii) reacting the compound of formula (C) from step 2 with a reducing agent in solvent in the presence of a catalyst to give the compound of formula (D)