Ammonia → (3-Fluoro-4-nitrophenyl)(3-(fluoromethyl)piperazin-1-yl)methanone

Temperature

0 °C

A stirred suspension of 3-fluoro-4-nitrobenzoic acid (2 g, 10.8 mmol) in dichloromethane (30 mL) was cooled to 0° C. (ice/water bath). Oxalylchloride (1.648 g, 12.97 mmol) was added followed by N-methylpyrrolidinone (1 mL) to achieve a solution. The reaction mixture was stirred at 0° C. for 1 hour and then was concentrated under reduced pressure. The residue was azeotroped with dichloromethane (×3). The residue was redissolved in dichloromethane (20 mL) and cooled to 0° C. before the addition of triethylamine (64.8 mmol, 6.56 g) and 1-(fluoromethyl)piperazine dihydrochloride (10.8 mmol, 2.064 g). The reaction mixture was allowed to warm to room temperature and stir for 1 hour before being applied to a strong cation exchange column. The crude product was released from the column using 2M ammonia in methanol and purified using silica chromatography (4% methanol/dichloromethane) to give the title compound (444 mg). MS (ESI) m/z 286.4 [M+H]+

1. concentrationwas concentrated under reduced pressure
2. customThe residue was azeotroped with dichloromethane (×3)
3. dissolutionThe residue was redissolved in dichloromethane (20 mL)
4. temperatureto warm to room temperature
5. stirringstir for 1 hour
6. custompurified

ORD record

ord-4d1ae29e647d44c6805a8881a2945ee2

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314091B2