Sodium Carbonate → 6-(3-Chlorophenyl)-4,4-dimethyl-1H-benzo[D][1,3]oxazin-2(4H)-one

HRID 1793344Notes

Reaction equation

HRID 1793344 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.[Cl:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:15][C:16]1[CH:21]=[C:20]([C:2]2[CH:14]=[CH:13][C:5]3[NH:6][C:7](=[O:12])[O:8][C:9]([CH3:11])([CH3:10])[C:4]=3[CH:3]=2)[CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 30630BrofoxineHCID 2734323(3-Chlorophenyl)boronic acid

Product 1

HCID 98823916-(3-Chlorophenyl)-4,4-dimethyl-1H-benzo[D][1,3]oxazin-2(4H)-oneYield 82.5%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one (1.5 g, 5.9 mmol), 3-chlorophenyl boronic acid (1.83 g, 11.7 mmol), tetrakis(triphenylphosphine)-palladium (0) (0.35 g, 0.3 mmol), and sodium carbonate (2.48 g, 23.4 mmol) in a mixture of DME and water (40 mL/10 mL) was degassed to remove the oxygen and then heated at 85° C. under a blanket of nitrogen for 3 hours. The reaction mixture was cooled to ambient temperature and quenched with a saturated aqueous ammonium chloride solution (20 mL). Ethyl acetate (50 mL) was added and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (3×15 mL). The combined organic layers were washed with brine and dried with MgSO4. The solvent was removed in vacuo and the residue was purified by silica gel flash chromatography (hexane:ethyl acetate/2:1) to afford 6-(3-chlorophenyl)-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one as a yellowish solid (1.4 g, 82%): mp 158–159° C.; 1H-NMR (DMSO-d6) δ 10.31 (s, 1H, D2O exchangeable), 7.75 (s, 1H), 7.61 (m, 3H), 7.46 (t, 1H, J=7.9 Hz), 7.39 (dd, 1H, J=7.0, 1.1 Hz), 6.96 (d, 1H, J=8.6 Hz), 1.68 (s, 6H); Anal. Calc. For C16H14ClNO2.0.1 H2O: C, 66.37, H, 4.94, N, 4.84. Found: C, 66.14, H, 4.61, N, 4.71.

Workup

  1. customwas degassed
  2. customto remove the oxygen
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. customquenched with a saturated aqueous ammonium chloride solution (20 mL)
  5. additionEthyl acetate (50 mL) was added
  6. customthe organic layer was separated
  7. extractionThe aqueous layer was extracted with ethyl acetate (3×15 mL)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried with MgSO4
  10. customThe solvent was removed in vacuo
  11. customthe residue was purified by silica gel flash chromatography (hexane:ethyl acetate/2:1)

Sources & evidence

ORD record
ord-c56b7eebb6a041479df5e59be7a069dc
Source dataset
uspto-grants-2006_07
Patent number
US07081457B2

Reaction notes

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