Trimethyl borate → (5-Ethoxy-2-fluoro-4-methoxyphenyl)boronic acid

Temperature

-78 °C

To a solution of 64D (324 mg, 1.1 mmol) in THF (5 mL) at −78° C. was slowly added n-BuLi (1.6 M in hexanes, 1.40 mL, 2.2 mmol). The reaction mixture was stirred at −78° C. for 20 min, followed by addition of trimethyl borate (0.31 mL, 2.8 mmol). The mixture was stirred at −78° C. for 3.0 h and then warmed up to rt over 18 h. It was quenched by addition of 1.0 N HCl (2.0 mL). After extraction with EtOAc, washing with a solution of Na2S2O3, brine and drying over Na2SO4, the crude product was purified by silica gel chromatography (eluting with 5% methanol in CH2Cl2) to give 64E (210 mg, 80% yield) as a white solid. 1H NMR (400 MHz, Methanol-d4) δ ppm 1.36 (t, J=6.81 Hz, 3H) 3.86 (s, 3H) 4.00 (q, J=7.03 Hz, 2H) 6.72 (d, J=10.11 Hz, 1H) 6.89 (d, J=5.27 Hz, 1H).

1. customat −78° C.
2. stirringThe mixture was stirred at −78° C. for 3.0 h
3. temperaturewarmed up to rt over 18 h
4. customIt was quenched by addition of 1.0 N HCl (2.0 mL)
5. extractionAfter extraction with EtOAc
6. washwashing with a solution of Na2S2O3, brine
7. dry with materialdrying over Na2SO4
8. customthe crude product was purified by silica gel chromatography (eluting with 5% methanol in CH2Cl2)

ORD record

ord-4237cf64bc584de1a9a3345d37c2fa14

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622585B2