1207852-96-7

1207852-95-6

1207852-96-7

Preparation of compound 25f: tert-butyl (2S,4α)-4-amino-2-(difluoromethyl)pyrrolidine-1-carboxylate 25e (1.5 g, 0.0057 mol) and triphenylphosphine (PPh3, 3.0 g, 0.0114 mol) were dissolved in a solvent mixture of tetrahydrofuran (THF, 50 mL) and water (5 mL), and stirred for 72 hours at room temperature. After completion of the reaction, the reaction mixture was concentrated under vacuum to give a residue. The residue was dissolved in ethyl acetate (EtOAc, 50 mL) and acidified by adjusting to pH~4 with 5% aqueous citric acid. The aqueous layer was separated and extracted with ethyl acetate (50 mL x 3). Subsequently, the aqueous layer was alkalized to pH~8 with solid sodium bicarbonate (NaHCO3), and then the alkalized aqueous layer was extracted with dichloromethane (50 mL × 3). The dichloromethane layers were combined, dried with anhydrous sodium sulfate (Na2SO4) and concentrated in vacuum to afford the target product (2S,4R)-4-amino-2-(difluoromethyl)-1-pyrrolidinecarboxylic acid-1,1-dimethylethyl ester 25f as a yellow oil (1.0 g, 76% yield).