METHYL 2-BROMOMETHYL-3-CHLORO-BENZOATE synthesis

Yield: 100%

Reaction Conditions:

with N-Bromosuccinimide;dibenzoyl peroxide in tetrachloromethane at 90; for 3.45 h;

Steps:

10c Methyl 2-(bromomethyl)-3-chlorobenzoate
A suspension of methyl 3-chloro-2-methylbenzoate obtained in Example 10b (1 g, 5.42 mmol), carbon tetrachloride (13.3 ml), N-bromosuccinimide (1.06 g, 5.96 mmol) and benzoyl peroxide (3.5 mg, 0.0108 mmol) was heated in a 90° C. oil bath under a nitrogen stream.
After three hours and 45 minutes, heating was completed, and the mixture was diluted with water, ethyl acetate and a saturated aqueous sodium bicarbonate solution.
The organic layer was washed with a saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered and concentrated to give the title compound (1.43 g, yield: 100%).
¹H-NMR (400 MHz, CDCl₃) δ ppm; 4.00 (3H, s), 5.12 (2H, s), 7.32 (1H, t, J=8 Hz), 7.58 (1H, dd, J=2, 8 Hz), 7.86 (1H, dd, J=2, 8 Hz).

References:

EISAI R&D MANAGEMENT CO., LTD.;YOSHIDA, Ichiro;OKABE, Tadashi;MATSUMOTO, Yasunobu;WATANABE, Nobuhisa;ONIZAWA, Yuji;OHASHI, Yoshiaki;HARADA, Hitoshi US2013/65925, 2013, A1 Location in patent:Paragraph 0338; 0339