4-Methylmorpholine → HCID 69290243, compound

Participants

Reaction Conditions

Reaction Steps

N-Methylmorpholine (0.048 mL) and isobutyl chloroformate (0.026 mL) were added to a stirred solution of (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (67 mg) in THF (1 mL) at −20° C. and the resultant mixture was stirred for 1 h. 3-Benzylhexahydro-1-methyl-2H-1,4-diazepin-2-one hydrochloride obtained in Step B above (48 mg) and N-methylmorpholine (0.024 mL) in DMF (1 mL) were added. The mixture was stirred for 30 min at −20° C. and for 36 h at ambient temperature, and then evaporated. The residue was treated with saturated aqueous ammonium chloride solution, extracted with ethyl acetate, and the organic extract evaporated. The product obtained was purified by preparative TLC (silica gel, methanol/concentrated ammonium hydroxide/dichloromethane 4.4:0.1:95.5) to obtain the coupled product as a mixture of diastereomers. The isomers were resolved by HPLC (ChiralPAK AD, 14% ethanol/bexane) and the faster eluting (R,S)-isomer and slower eluting (R,R)-isomer were collected.

Provenance & Evidence