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

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.

1. distillationThe solvent was distilled off under reduced pressure
2. dissolutionthe resulting residue was dissolved in dichloromethane (100 mL)
3. stirringby stirring at room temperature for 4.5 hours under nitrogen atmosphere
4. extractionextraction
5. washThe organic layer was washed with saturated brine
6. dry with materialsubsequently dried over anhydrous magnesium sulfate
7. distillationThe solvent was distilled off under reduced pressure
8. customthe resulting residue was purified
9. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=40%-50%)

ORD record

ord-aa4bbec25071436d9451d45aa6d77d7d

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08017610B2