Hydrochloric Acid → 1-(3,4-Difluorobenzoyl)azetidine

Participants

Reaction Steps

Commercially available 3,4-difluorobenzoic acid (3.00 g, 19.0 mmol) was dissolved in dichloromethane (50 mL), and N,N-dimethylformamide (0.10 mL) was added, followed by dropwise addition of oxalyl chloride (1.98 mL, 22.8 mmol) and stirring at room temperature overnight under nitrogen atmosphere. The solvent was distilled off under reduced pressure, and the resulting residue was dissolved in dichloromethane (100 mL), and azetidine hydrochloride (2.27 g, 24.2 mmol) and triethylamine (6.60 mL, 47.4 mmol) were added, followed by stirring at room temperature for 4.5 hours under nitrogen atmosphere. 0.5N hydrochloric acid (100 mL) was added, and extraction was carried out with dichloromethane (100 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=40%-50%) to afford the desired compound (600 mg, yield 16%) as a colorless liquid.

Provenance & Evidence