2-BROMOMETHYL-5-(TRIFLUOROMETHYL)PHENYLBORONIC ACID PINACOL ESTER synthesis

Yield:1030832-72-4 90%

Reaction Conditions:

with N-Bromosuccinimide;2,2'-azobis(isobutyronitrile) in tetrachloromethane; for 4.5 h;Heating / reflux;Irradiation;

Steps:

18.3

6-Methyl-3- (trifluoromethyl) phenylboronic acid pinacol ester (24b, 3.Og, 10 mmol) and 60 ml CCl₄ were placed in 500 ml round-bottom flask. NBS (1.9, 10.5 mmol, 1.05 eq) and AIBN (0.02g, 0.14 mmol, 0.014 eq) were added and the reaction mixture was refluxed for 4.5h in the presence of 75W incandescent bulb. After 4.5h the solution was cooled down to room temperature allowing the succinimide to precipitate out. The solid was filtered off. The solvent was removed and oily product was collected. The crude product was purified by triturating with hexane which resulted in 80% pure product (25b, 3.6g, 95% yield).Structure determination:RP-HPLC Conditions: HP 1100 HPLC chromatograph, Waters 3.9 x 150 mm NovaPak HR C18 column with guard column, 0.010 mL injection, 1.5 mL/min, 1.500 mL injection loop, 254 nm detection, A = water (0.1% v/v TFA) and B = MeCN (0.1% v/v TFA), gradient 10% B 1 min, 10-80% B over 9 min, 80-100% B over 1 min, 100 %B 1 min, retention time 8.7 min (for boronic acid) and 12.4 min (for pinacol ester).¹H NMR (400 MHz, CDCl₃): δ 1.38 (s, 12H), 4.91 (s, 2H), 7.50 (d, IH), 7.64 (d, IH), 8.06 (s, IH).

References:

WO2008/66921,2008,A2 Location in patent:Page/Page column 71