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

HRID 50662Notes

Reaction equation

HRID 50662 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]2[NH:6][C:7](=[O:12])[O:8][C:9]([CH3:11])([CH3:10])[C:4]=2[CH:3]=1.[Li]CCCC.CCCCCC.[B:26](OC(C)C)([O:31]C(C)C)[O:27]C(C)C>C1COCC1>[CH3:10][C:9]1([CH3:11])[C:4]2[CH:3]=[C:2]([B:26]([OH:31])[OH:27])[CH:14]=[CH:13][C:5]=2[NH:6][C:7](=[O:12])[O:8]1

Participants

6

Reactant 4

HCID 8058HexaneHCID 21531Triisopropyl borateHCID 30630BrofoxineHCID 178418339Butyllithium

Product 1

HCID 10987806(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)boronic acidYield 81.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-01eaafa979e74a54a3a906bcfa16b476
Source dataset
uspto-grants-2004_03
Patent number
US06713478B2

Reaction notes

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