162744-59-4

4-Bromo-2,6-difluorobenzyl alcohol is an organic intermediate. It has been reported that 4-bromo-2,6-difluorobenzyl alcohol can be used to prepare RET inhibitors.

4-Bromo-2,6-difluorobenzyl alcohol can be used to prepare RET inhibitors.

4-Bromo-2,6-difluorobenzyl alcohol can be obtained by reducing the carboxyl group from 4-bromo-3,5-difluorobenzoic acid.

General procedure for the synthesis of 4-bromo-2,6-difluorobenzenemethanol from 2,6-difluoro-4-bromobenzoic acid: to a solution of 2,6-difluoro-4-bromobenzoic acid (5 g, 21.10 mmol) in tetrahydrofuran (THF, 100 mL) was slowly added borane (BH3). Dimethyl sulfide (DMS, 20.03 mL, 211 mmol) was added dropwise at room temperature. The reaction mixture was stirred at 60 °C for 16 hours. After confirming complete consumption of the feedstock by liquid chromatography-mass spectrometry (LCMS) analysis, the reaction was quenched with methanol (MeOH). The solvent was evaporated under reduced pressure to afford 4-bromo-2,6-difluorobenzenemethanol as a white solid (4.5 g, 20.02 mmol, 95.2% yield), which could be used in subsequent reactions without further purification. Electrospray liquid chromatography-mass spectrometry (ES-LCMS) analysis showed m/z 222.1 ([M+H]+).

[1] Patent: US2014/275111, 2014, A1. Location in patent: Paragraph 0371; 0372
[2] Patent: WO2014/141187, 2014, A1. Location in patent: Page/Page column 81; 82
[3] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 10, p. 3258 - 3262