1-(Bromomethyl)-3-methoxy-5-(trifluoromethyl)benzene, 3-(Bromomethyl)-5-(trifluoromethyl)phenyl methyl ether synthesis

Yield: 91%

Reaction Conditions:

with N-Bromosuccinimide;triphenylphosphine in dichloromethane at 0 - 20; for 1 h;

Steps:

71.15
To a solution of (3-methoxy-5-trifluoromethyl-phenyl)-methanol (1 mmol, 206 mg) and triphenylphosphine (1.5 mmol, 392 mg) in dichloromethane (10 mL) which is cooled to 0 ⁰C is added NBS (1.5 mmol, 266 mg) under nitrogen. The solution is allowed to warm to rt and stirred for 1 hour. The solution is added water, then extracted with ethyl acetate. The combined organic layer is washed with brine, dried over Na₂SO₄, filtrated, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent: hexane / EtOAc) to give 1-bromomethyl-3-methoxy-5-trifluoromethyl-benzene (245 mg, 91%); ESI-MS m/z: 189 [M-Br+1] Retention time 1.76 min (condition A).

References:

NOVARTIS AG;NOVARTIS PHARMA GMBH WO2008/9435, 2008, A1 Location in patent:Page/Page column 161-162