Methyl-(2S,3S)-1-{[(3-chloro-4-cyano-2-methylphenyl)amino]-carbonyl}-3-(tert-butyl-dimethylsilanyloxy)-pyrrolidine-2-carboxylate → (2R,3S)-N-(3-Chloro-4-cyano-2-methylphenyl)3-(tert-butyldimethylsilanyloxy)-2-(hydroxymethyl)pyrrolidine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of compound 55B (300 mg, 0.66 mmol) in anhydrous THF (6.7 mL) at −25° C. was added 1 N LAH in THF (1.34 mL, 1.34 mmol) over a period of 10 min. The solution was then warmed to 0° C. and stirred for 2.0 h before quenching with H2O (0.05 mL), 15% NaOH (0.05 mL) and H2O (0.16 mL). After warming to rt, the mixture was extracted with EtOAc (2×40 mL). The combined organic phases were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The resultant off-white solid was chromatographed (silica gel; EtOAc/hexane gradient) to yield the title compound (217.2 mg, 78%) as a white solid, mp 174-176° C. HPLC: 3.23 min (retention time) (Conditions: YMC S-5 C-18 (4.6×50 mm), eluting with 0-100% B, 4 min gradient. (A=90% H2O-10% CH3CN-0.1% TFA and B=10% H2O-90% CH3CN-0.1% TFA); Flow rate at 4 mL/min. UV detection at 220 nm. Chiral HPLC: retention time=7.11 min (96.1%); Conditions: AD (4.6×250 mm); Eluted with 20% isopropanol in heptane for 30 min at 1 mL/min. MS (ES) m/z 424 [M+H]+.

Provenance & Evidence