[Synthesis]
General procedure for the synthesis of 4-(2-hydroxypropan-2-yl)phenylboronic acid from triisopropyl borate and 2-hydroxy-2-(4-bromophenyl)propane:
1. n-BuLi (2.5 M hexane solution, 1.00 mL, 2.5 mmol) was slowly added dropwise to a THF (20 mL) solution of 2-hydroxy-2-(4-bromophenyl)propane (0.50 g, 2.33 mmol) at -78 °C.
2. After 1.5 hours of reaction, n-BuLi (0.95 mL, 2.38 mmol) was added and stirring was continued at -78 °C for 2 hours.
3. triisopropyl borate (1.08 mL, 4.66 mmol) was added and the reaction mixture was slowly warmed to room temperature and stirred for 3 days.
4. Upon completion of the reaction, the reaction was quenched by the addition of 1N HCl and extracted with EtOAc 3 times.
5. The organic phases were combined, washed with brine, dried over anhydrous MgSO4 and concentrated under reduced pressure to give 0.29 g of crude product.
6. purified by column chromatography, first eluted with 50% EtOAc/hexane, then eluted with 10% MeOH/EtOAc to obtain partially purified product.
7. Final grinding with ether gave 51 mg (13% yield) of the target product 4-(2-hydroxypropan-2-yl)phenylboronic acid (PP33) as a white solid.
NMR data (MeOH-d4): δ 7.67 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 7.88 Hz, 1H), 7.45-7.40 (m, 2H), 1.97 (s, 6H). |