Water → HCID 58748302, compound

Participants

Reaction Steps

89.2 A mixture of 200 mg (2S,4R)-4-[(5-chloro-thiophene-2-carbonyl)-amino]-2-formyl-pyrrolidine-1-carboxylic acid tert-butyl ester, 90 mg 2,2-difluorethyl amine (solution in 1 ml THF) and 0.33 ml tetraisopropyl orthotitanate was stirred at r.t. for 1 h 30. The mixture was diluted with 1.5 ml ethanol and 35 mg NaBH3CN was added. Stirring at r.t. was continued for 18 h. Then, 0.5 ml H2O was added and stirring was continued for 30 min. The mixture was concentrated. The crude product was purified by column chromatography (silica gel; gradient: cyclohexane->cyclohexane/EtOAc 3:7) to give 105 mg (2S,4R)-4-[(5-chloro-thiophene-2-carbonyl)-amino]-2-[(2,2-difluoro-ethylamino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester as white amorphous solid. MS 424.0 ([M+H]+)

Provenance & Evidence