3-CYCLOPROPYL-5-(TRIFLUOROMETHYL)ANILINE synthesis

Yield:1057079-57-8 55%

Reaction Conditions:

palladium diacetate;tricyclohexylphosphine in water;toluene at 100; for 2 h;Inert atmosphere;

Steps:

30.a

Example 30: Synthesis of c/s-N-(3-cyclopropyl-5-(trifluoromethyl)phenyl)-3-ethyl-4- methyl-l-(2,6-dimethyIphenyl)-5-oxopyrrolidine-3-carboxamide[0167] a) A 40 mL vial was charged with 3-amino-5-bromobenzotrifluoride (275 mg, 1.15 mmol), cyclopropylboronic acid (128 mg, 1.5 mmol), Pd(OAc)₂ (13 mg, 0.06 mmol), triclyclohexylphosphine (38 mg, 0.13 mmol), and K₃P0₄ (488 mg, 2.3 mmol). The vial was subsequently sealed with a septum-lined screw cap and purged with nitrogen, followed by the addition of degassed toluene (4 mL) and degassed water (1 mL). After stirring the reaction mixture for 2 h at 100 °C, the mixture was diluted in ethyl acetate (50 mL) and the organics were washed with brine, dried (MgS0₄), and concentrated in vacuo. The residue was purified by flash chromatography (Si0₂, 10-40% EtOAc/hexanes) to give the desired product in 55% yield (126 mg). LC-MS R_t (retention time): 2.46 min, MS: (ES) m/z 202 (M+H⁺). [0168]

References:

WO2011/35332,2011,A1 Location in patent:Page/Page column 69