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

Temperature

-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 solution was slowly warmed to ambient temperature and quenched with 1N aqueous hydrochloric acid solution (60 mL). Ethyl acetate (100 mL) was added, the organic layer was separated, and the 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 solution was slowly warmed to ambient temperature
3. customquenched with 1N aqueous hydrochloric acid solution (60 mL)
4. additionEthyl acetate (100 mL) was added
5. customthe organic layer was separated
6. extractionthe aqueous 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 record

ord-88ee3f428b7442939536d23f7b4edcc7

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08466146B2