Synthesis
[Step 2] Synthesis of (4-bromo-2-(trifluoromethoxy)phenyl)methanol: To a solution of 4-bromo-2-(trifluoromethoxy)benzaldehyde (16 g, 59 mmol) in methanol (0.23 L) was added sodium borohydride (2.4 g, 63 mmol) in batches at -10 °C. The reaction solution was stirred at -10 °C for 10 min before acetone (10 mL) and 1N hydrochloric acid (10 mL) were added sequentially to quench the reaction. The reaction mixture was concentrated under reduced pressure and water was added to the residue and extracted with ethyl acetate. The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (elution gradient: hexane/ethyl acetate = 50:1 → 1:1) to afford 15 g (91% yield) of the title compound (4-bromo-2-(trifluoromethoxy)phenyl)methanol (hereinafter referred to as Reference Example Compound 2).
References
[1] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 9, p. 1311 - 1316
[2] Patent: EP2832724, 2015, A1. Location in patent: Paragraph 0124
[3] Patent: US5968938, 1999, A
[4] Patent: US6090805, 2000, A
[5] Patent: WO2010/96722, 2010, A1. Location in patent: Page/Page column 60-62
