Hydrogen Peroxide → (S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(2-fluoro-4-(trifluoromethyl)phenyl)acetic acid

Participants

Reaction Steps

To a solution of LiOH—H2O (0.3177 g, 7.570 mmol) in THF/water (2:1, 240 mL) was added 30% H2O2(0.91 mL, 9.46 mmol) and the soln stirred at RT for 10 min. The solution was cooled to 0° C. and a solution of 320 (2.19 g, 3.785 mmol) in THF (10 mL) was added. The reaction was stirred at 0° C. for 2 h then warmed to RT and stirred overnight. The reaction was then cooled to 0° C. and treated with 1M Na2SO3 (10 mL) and stirred for 10 min then warmed to RT and stirred for 10 min. The reaction was concentrated and extracted with EtOAc (2×20 mL). The aqueous phase was acidified with H2SO4 to pH ca. I-2 and extracted with DCM (2×20 mL). The organic extracts were concentrated and the crude product purified C18 preparative MPLC (Analogix 200 g C18 column) to afford 1.321 g (83.2%) of (S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(2-fluoro-4-(trifluoromethyl)phenyl)acetic acid (322).

Provenance & Evidence