Sodium bis(trimethylsilyl)amide → (R)-4-((R)-1-(6-chloro-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Participants

Reaction Steps

Under Ar, NaHMDS (1.0 M in THF, 0.96 mL, 0.96 mmol) was added over 30 s to a solution of (R)-4-((R)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.04 (255 mg, 0.968 mmol) in DMF (3 mL). After stirring 10 min, the resulting mixture was added over ca. 45 s to a cooled (−20° C.) solution of 6-chloro-3-(difluoromethyl)-4-(methylsulfonyl)-3H-imidazo[4,5-c]pyridine (215 mg, 0.763 mmol) in DMF (3 mL). After stifling 15 min, the reaction was quenched with saturated NH4Cl (3 mL) and was diluted with EtOAc (20 mL) and water (20 mL). The phases were separated, and the organic layer was washed with water (30 mL) and brine (30 mL). The organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (20-45% acetone in hexanes) to provide (R)-4-((R)-1-(6-chloro-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one. LCMS-ESI+ (m/z): [M+H]+ calcd for C22H24ClF2N4O3: 465.2; found: 464.9.

Provenance & Evidence