Sodium Hydroxide → (S)-[6-(3-Fluoro-4-methylphenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]acetic acid

Participants

Reaction Steps

To a stirred solution of (S)-6-(3-fluoro-4-methylphenyl)-3,3-dimethylpiperidin-2-one from Step A (80 mg, 0.340 mmol) in DMF (3 mL) at ambient temperature was added NaH (19 mg of a 60% dispersion in oil, 0.476 mmol). After 15 min, methyl bromoacetate (0.051 mL, 0.544 mmol) was added and the mixture was stirred for 16 h. Sodium hydroxide (0.061 mL of a 10 M solution, 0.612 mmol) was added and the mixture stirred for 2 h. The crude product was purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. The compound was further purified by SFC, utilizing a ChiralPak AD column and eluting with CO2:MeOH—91:9, to give the title compound. MS: m/z=294 (M+1).

Provenance & Evidence