Lithium Hydroxide → HCID 24762809, compound

Participants

Reaction Steps

To a solution of (R)-4-[3-(2,6-dichloro-4-trifluoromethanesulfonyloxy-benzyl)-2-oxo-pyrrolidin-1-yl]-4,5,6,7-tetrahydro-indazole-1-carboxylic acid tert-butyl ester and (R)-4-[3-(2,6-dichloro-4-trifluoromethanesulfonyloxy-benzyl)-2-oxo-pyrrolidin-1-yl]-4,5,6,7-tetrahydro-indazole-2-carboxylic acid tert-butyl ester (Preparation 105) (0.90 g, 1.39 mmol) in THF (35 mL), add 2M sodium carbonate (2.1 mL, 2.78 mmol) and 4-fluorophenylboronic acid (0.23 g, 1.64 mmol). Degas the mixture using a nitrogen gas dispenser for 5 minutes. Add Tetrakis(triphenylphosphine)palladium (0.081 g, 0.070 mmol), bring the reaction mixture to 80° C., and stir under nitrogen for 1 hour. Cool the reaction to room temperature and then treat with 2M aqueous LiOH (14 mL) and stir at room temperature for 1 hour. Partition the mixture between ethyl acetate and water; separate the organic, dry over sodium sulfate, filter and concentrate to afford crude product, and then purify by flash chromatography (gradient, 0 to 10% methanol in dichloromethane) to afford 0.57 g (89%) of the desired product as a mixture of regioisomers. LCMS: 458 (M+H).

Provenance & Evidence