4-Chloro-2-methylphenylboronic acid pinacol ester synthesis

Yield: 97%

Reaction Conditions:

Stage #1:2,3-dimethyl-2,3-butane diol;4-chloro-2-methylphenylboronic acid in diethyl ether
Stage #2: with magnesium sulfate in diethyl ether at 20; for 24 h;

Steps:

20.1
4-Chloro-2-methylphenylboronic acid (5.Og, 29 mmol) and 100 ml of Diethyl ether were placed in round-bottom flask. Then pinacol was added (3.43, 29 mmol, leq) and the resulting reaction mixture was stirred for couple of minutes until the solution became clear. Finally, MgSO,_? (6.98, 58 mmol, 2eq) was added and the solution was allowed to stir at ambient temperature, under N₂ balloon overnight. After 24h the reaction was worked up. MgSO₄ was filtered off and washed with Et₂O. Organic layer was collected and the solvent was then removed. Pure product (7.2g, 97% yield) was obtained as a white powder.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 12.6 min. ¹H NMR (400 MHz, CDCl₃): δ 1.33 (s, 12H), 2.50 (s, 3H), 7.14 (m, 2H) , 7.68 (d, IH) .

References:

SENSORS FOR MEDICINE AND SCIENCE, INC. WO2008/66921, 2008, A2 Location in patent:Page/Page column 78-79