Benzoic Acid → 4-bromo-N-cyclopropyl-2-(trifluoromethyl)benzamide

1.50 g (1 eq, 5.57 mmol) of 4-bromo-2-(trifluoromethyl)benzoic acid (synthesis analogous to EP1445253 Yamanouchi Pharmaceutical Co. by bromination of the benzoic acid) were dissolved in 5 ml of dichloromethane. Then 954 mg (1.0 eq, 5.57 mmol) of 6-chlorohydroxybenzotriazole, 1.28 g (1.2 eq, 6.69 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and 1.45 ml (1.5 eq, 8.63 mmol) of N-ethyldiisopropylamine were added thereto, and the mixture was stirred at RT for 20 min. Subsequently, 477 mg (1.5 eq, 8.36 mmol) of cyclopropylamine were added thereto, and the reaction mixture was stirred at room temperature for 12 h. Thereafter, the mixture was concentrated under reduced pressure and the crude product dissolved in ethyl acetate (EA). The solution was washed 2× with buffer solution (0.5 M phosphate buffer pH=7) and then dried over MgSO4. The purification was effected by means of silica gel chromatography with the eluent cyclohexane/ethyl acetate (EA) (0% EA to 100% EA). This gives 831 mg (48%) of 4-bromo-N-cyclopropyl-2-(trifluoromethyl)benzamide as a white solid.

1. stirringthe reaction mixture was stirred at room temperature for 12 h
2. concentrationThereafter, the mixture was concentrated under reduced pressure
3. dissolutionthe crude product dissolved in ethyl acetate (EA)
4. washThe solution was washed 2× with buffer solution (0.5 M phosphate buffer pH=7)
5. dry with materialdried over MgSO4
6. customThe purification

ORD record

ord-9474aab1eb39429d9dca96548ef438c0

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889878B2