Synthesis
Step 1: Preparation of 2-(3-bromophenyl)-2-propanol (27)
Methyl 3-bromobenzoate (4.3 g, 20 mmol) dissolved in 25 mL of anhydrous THF was added dropwise over 10 min to 75 mL of ether solution containing 75 mmol of methylmagnesium bromide under nitrogen protection. After the dropwise addition, the reaction mixture was slowly warmed to room temperature and stirred for 3.5 hours. Subsequently, the reaction system was cooled to 0°C and the reaction was quenched by slow addition of 10% aqueous HCl solution. The acidified mixture was extracted with ethyl acetate (2×) and the organic phases were combined and washed sequentially with 1N NaHCO3 solution and saturated saline. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography using 15% ethyl acetate/heptane as eluent to afford 4.00 g (18.6 mmol, 93%) of 2-(3-bromophenyl)-2-propanol (27) as a pale yellow oil.
References
[1] Patent: WO2005/95326, 2005, A2. Location in patent: Page/Page column 189-190
[2] Journal of Organic Chemistry, 1960, vol. 25, # 10, p. 1691 - 1693
[3] Patent: WO2005/70932, 2005, A2. Location in patent: Page/Page column 51
[4] Patent: WO2015/89067, 2015, A1. Location in patent: Page/Page column 122
[5] Patent: US9126993, 2015, B2. Location in patent: Page/Page column 50
