1-Hydroxybenzotriazole → [(R)-2-(3-fluoro-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 (0.40 g, 1.82 mmol), 3-fluoroazetidine hydrochloride (204 mg, 1.82 mmol), HBTU (989 mg, 2.74 mmol), and HOBt (375 mg, 2.74 mmol). Then added DMF (3.6 mL) followed by N,N-diisopropylethylamine (1.27 mL, 7.3 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 was dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0-50% EtOAc) to afford 267 mg (53%) of [(R)-2-(3-fluoro-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-carbamic acid tert-butyl ester as a white solid.

Provenance & Evidence