Boron tribromide → 3-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenol

Participants

Reaction Steps

A stirred solution of (R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-1-(3-methoxyphenylsulfonyl)-2-methylpiperazine (2.22 g, 5.13 mmol) in anhydrous dichloromethane (60 mL) was cooled down to −50° C. (acetone+dry ice bath). BBr3 (1M in CH2Cl2) was added dropwise via addition funnel while keeping the temperature between −50° C. and −55° C. Then the reaction mixture was stirred at −50° C. to −20° C. for 3 hours. Reaction was complete as determined by TLC. The reaction mixture was quenched with water and diluted with dichloromethane. pH was adjusted to 7 using saturated NaHCO3 (aqueous) and it was allowed to stir for 20 minutes. The layers were separated; the organic layer was dried over MgSO4 and concentrated. The reaction was repeated in 2.85 g scale. The combined crud products were purified via flash column chromatography to yield 3-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenol in 96% yield (4.07 g) as a white solid. HRMS: calcd for C18H18F4N2O3S+H+, 419.10470. found (ESI-FTMS, [M+H]1+), 419.104. HPLC Method 1: room temperature, 6.318 min, 100%, HPLC Method 2: room temperature, 7.220 min, 99.48%.

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