(3,5-DIFLUORO-2-HYDROXY-PHENYL)BORONIC ACID synthesis

Yield:1150114-51-4 72%

Reaction Conditions:

Stage #1: (3,5-difluoro-2-methoxyphenyl)boronic acidwith boron tribromide in dichloromethane at 0; for 2 h;
Stage #2: with water in dichloromethane;Cooling with ice;

Steps:

122

Intermediate 122: (3,5-difluoro-2-hydroxyphenyl)boronic acid; A solution of boron tribromide (1 12 ml_, 1 M in DCM, 112 mmol, 3 equiv.) was added to a solution of commercially available [3,5-difluoro-2-(methyloxy)phenyl]boronic acid (7 g, 37.4 mmol) in DCM (100 ml.) at 0⁰C. The reaction mixture was stirred at this temperature for 2h before being poured into iced water (150 ml_). The aqueous layer was extracted with DCM and the resulting organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was triturated in cyclohexane to give the title compound (4.7 g, 72% yield) as a off-white solid. 1 H NMR (CD₃OD, 300 MHz) δ 6.86 (m, 1 H), 6.66 (m, 1 H). LCMS: m/z 173, (M-H)^", Rt 2.30 min.

References:

WO2010/15652,2010,A2 Location in patent:Page/Page column 74