Diisopropylethylamine → [(R)-2-(3-cyano-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-carbamic acid tert-butyl ester

Participants

Reaction Steps

A 25 mL round-bottomed flask was charged with (R)-2-tert-butoxycarbonylamino-3-methoxy-propionic acid (0.475 g, 2.17 mmol), azetidine-3-carbonitrile hydrochloride (314 mg, 2.65 mmol) and HATU (832 mg, 2.19 mmol). Then added DMF (3.6 mL) followed by N,N-diisopropylethylamine (1.5 mL, 8.67 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (30 mL). The organic layer was washed once with saturated NaHCO3 and water. The combined aqueous layers were back extracted with EtOAc (25 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0-100% EtOAc) to afford 288 mg (47%) of [(R)-2-(3-cyano-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-carbamic acid tert-butyl ester as a viscous colorless oil.

Provenance & Evidence