Triisopropyl borate → [5-Methoxy-2-(trifluoromethoxy)phenyl]boronic acid

Temperature

-70 °C

To a stirred solution of 2-Bromo-4-methoxy-1-trifluoromethoxy-benzene (Preparation 59, 19.0 g, 73.9 mmol) in anhydrous tetrahydrofuran (400 ml) was added n-butyl lithium (2.5M solution in hexanes, 44.2 ml, 110.9 mmol) while maintaining the temperature below −70° C. under an atmosphere of nitrogen. The resulting solution was stirred at −70° C. for 1 hour. Tri-isopropyl borate (20.9 g, 110.9 mmol) was added and the mixture stirred at −70° C. for an additional 2 hours. The reaction mixture was quenched with saturated ammonium chloride aqueous solution (400 ml). The resulting mixture was acidified to pH˜5 by addition of hydrochloric acid (1N aqueous solution). The layers were separated and the organic layer was washed with water (200 ml) then dried over anhydrous MgSO4 (s), filtered and evaporated in vacuo. Residue was purified by recrystallization from ethyl acetate:petroleum ether (2 ml:50 ml) to afford the title compound as a white solid (7.5 g, 43%).

1. temperaturewhile maintaining the temperature below −70° C. under an atmosphere of nitrogen
2. stirringthe mixture stirred at −70° C. for an additional 2 hours
3. customThe reaction mixture was quenched with saturated ammonium chloride aqueous solution (400 ml)
4. additionThe resulting mixture was acidified to pH˜5 by addition of hydrochloric acid (1N aqueous solution)
5. customThe layers were separated
6. washthe organic layer was washed with water (200 ml)
7. dry with materialthen dried over anhydrous MgSO4 (s)
8. filtrationfiltered
9. customevaporated in vacuo
10. customResidue was purified by recrystallization from ethyl acetate

ORD record

ord-f29a2c80d1df4f6488875795188f9afd

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08134007B2