Hexane → (4,4-Dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)boronic acid

Temperatur

-78 °C

To a solution of 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one (2 g, 7.8 mmol) in anhydrous THF (60 mL) was added a solution of n-BuLi in hexane (10 M, 2.4 mL, 24 mmol) at −78° C. under nitrogen. After stirring at −78° C. for 30 minutes, a slurry was obtained and treated with triisopropyl borate (6.5 mL, 28 mmol). The reaction medium was slowly warmed to ambient temperature and quenched with 1N aqueous hydrochloric acid solution (60 mL). Ethyl acetate (100 mL) was added and organic layer was separated, and aqueous layer was extracted with ethyl acetate (3×60 mL). The combined organic layer was washed with brine and dried with MgSO4. The solvent was removed in vacuo and the residue was purified by a silica gel flash chromatography (ethyl acetate:hexane/2:1) to afford (1,4-dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid as a white solid (1.4 g, 81%): mp 249-250° C.; 1H-NMR (DMSO-d6) δ 10.21 (s, 1H, D2O exchangeable), 7.90-7.95 (br s, 2H, D2O exchangeable), 7.67 (m, 2H), 6.79 (d, 1H, J=7.8 Hz), 1.61 (s, 6H) MS (ESI) m/z 222 ([M+H]+, 87%).

1. customa slurry was obtained
2. temperatureThe reaction medium was slowly warmed to ambient temperature
3. customquenched with 1N aqueous hydrochloric acid solution (60 mL)
4. additionEthyl acetate (100 mL) was added
5. customorganic layer was separated
6. extractionaqueous layer was extracted with ethyl acetate (3×60 mL)
7. washThe combined organic layer was washed with brine
8. dry with materialdried with MgSO4
9. customThe solvent was removed in vacuo
10. customthe residue was purified by a silica gel flash chromatography (ethyl acetate:hexane/2:1)

ORD-Eintrag

ord-01eaafa979e74a54a3a906bcfa16b476

Quelldatensatz

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06713478B2