Thionyl Chloride → Benzyl 3-[(4-cyclobutylpiperazin-1-yl)carbonyl]azetidine-1-carboxylate

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Reaction Steps

To a stirred solution of 1-[(benzyloxy)carbonyl]azetidine-3-carboxylic acid (250 mg, 1.06 mmol) in dichloromethane (2 mL) at RT was added SOCl2 (115 μL, 1.59 mmol). The mixture was stirred for 18 hours before volatiles were removed at reduced pressure. The residue was then dissolved in dichlormethane (3 mL) and 1-cyclobutylpiperazine (115 mg, 1.28 mmol) followed by DIPEA (940 μL, 5.31 mmol) added. The mixture was stirred at RT for 4 hours and then quenched with saturated aq. NaHCO3 (1 mL). The aqueous phase was extracted with dichloromethane (2×5 mL), the organics combined, washed with brine (2 mL), dried (MgSO4), filtered and concentrated at reduced pressure to give the title compound (130 mg, 34%), after purification by silica FCC (97.5:2.25:0.25 DCM/MeOH/NH3).

Provenance & Evidence