4-Methylmorpholine → [(S)-1-(4-Cyano-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester

Participants

Reaction Steps

A mixture of 4-amino-3-phenylaminobenzonitrile (490 mg, 2.34 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (490 mg, 2.57 mol), HOAt (380 mg, 2.79 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (540 mg, 2.81 mol) and 4-methylmorpholine (560 μL, 5.15 mmol) in THF (5 mL) was stirred at RT for 48 h under an argon atmosphere. The crude reaction mixture was then partitioned between EtOAc and a saturated solution of NaHCO3. The aqueous phase was further extracted with EtOAc and the combined organic layers were washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% EtOAc in DCM) affording [(S)-1-(4-Cyano-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester as a cream foam (800 mg, 89%). LCMS: RT 3.62 min [M+H]+ 381.2.

Provenance & Evidence