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

HRID 50663

Reaction equation

HRID 50663 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 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 a 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. customorganic 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 a silica gel flash chromatography (hexane:ethyl acetate/2:1)

Sources & evidence

ORD record
ord-550af3a1ab9848e9a981ac94b166eac1
Source dataset
uspto-grants-2004_03
Patent number
US06713478B2

Linked notes

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