Yield: 85%

Reaction Conditions:

with bromine;triphenylphosphine in ethanol;dichloromethane at 0; for 0.5 h;

Steps:

Step 1:
4-(bromomethyl)-1-chloro-2-fluorobenzene
Step 1:
4-(bromomethyl)-1-chloro-2-fluorobenzene
,To a solution of triphenylphosphine (27.8 g, 0.103 mol) in CH₂Cl₂ (200 mL), bromine (16.5 g, 0.103 mol) was added dropwise at 0°C under stirring.
Upon completion of the addition, the resultant was stirred for 10 minutes. (4-Chloro-3-fluorophenyl)methanol (15.8 g, 0.098mol) was then added.
The resultnat was stirred for 30 minutes.
The reaction was quenched with ethanol, poured into saturated sodium bicarbonate solution, and extracted with CH₂Cl₂.
The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography to give 4-(bromomethyl)-1-chloro-2-fluorobenzene (18.6 g, 85% yield).
¹H-NMR (400 MHz, CDCl₃):δ= 7.27 (t, J = 7.9Hz, 1H), 7.10 (dd, J= 7.9 Hz, 2.1 Hz, 1H), 7.04-6.99 (m, 1H), 4.32 (s, 2H).

References:

Chia Tai Tianqing Pharmaceutical Group Co.,Ltd;Centaurus BioPharma Co., Ltd.;Lianyungang Runzhong Pharmaceutical Co., Ltd.;XIAO, Dengming;XU, Xinhe;LIU, Xijie;HU, Yuandong;YU, Honghao;LIU, Zhihua;PENG, Yong;SUN, Yinghui;LUO, Hong;KONG, Fansheng;HAN, Yongxin;SUN, Jian EP2952510, 2015, A1 Location in patent:Paragraph 0185