Ammonium Chloride → 6-(3-Methoxyphenyl)-4-methyl-4-trifluoromethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one

HRID 50704Notes

Reaction equation

HRID 50704 reaction equation
Cl[C:2]1[CH:17]=[CH:16][C:5]2[NH:6][C:7](=[O:15])[O:8][C:9]([CH3:14])([C:10]([F:13])([F:12])[F:11])[C:4]=2[CH:3]=1.[CH3:18][O:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl-].[NH4+]>O1CCOCC1.C(OCC)(=O)C>[CH3:18][O:19][C:20]1[CH:25]=[C:24]([C:2]2[CH:17]=[CH:16][C:5]3[NH:6][C:7](=[O:15])[O:8][C:9]([CH3:14])([C:10]([F:13])([F:12])[F:11])[C:4]=3[CH:3]=2)[CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 2734370(3-Methoxyphenyl)boronic acid2×HCID 98350626-Chloro-4-methyl-4-trifluoromethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one

Product 1

HCID 102686936-(3-Methoxyphenyl)-4-methyl-4-trifluoromethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-oneYield 20%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 6-chloro-4-methyl-4-trifluoromethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one (0.2 g, 0.75 mmol), 3-methoxyphenyl boronic acid (0.13 g, 0.9 mmol), potassium phosphate (0.23 g, 1.1 mmol), and nickel (II) (diphenylphosphino)ferrocenyl dichloride (52 mg, 0.076 mmol) in anhydrous dioxane was subject to a blanket of nitrogen to remove oxygen and heated at 95° C. under nitrogen for 48 hours. Another portion of 3-methoxyphenyl boronic acid (0.3 g, 0.9 mmol) and nickel (II) (diphenylphosphino)ferrocenyl dichloride (52 mg, 0.076 mmol) was added and the reaction solution was heated at 95° C. under nitrogen for 48 hours. The reaction solution was cooled to room temperature. Saturated aqueous ammonium chloride solution (30 mL) and ethyl acetate (50 mL) was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic layer was washed with brine and dried (MgSO4). After removal of solvent, the residue was purified by a flash chromatography (silica gel, hexane:ethyl acetate/4:1) to afford the title compound as a white solid (50 mg, 20%): mp 178-179° C.; 1H-NMR (DMSO-d6) δ 10.85 (bs, 1H, D2O exchangeable), 7.73 (m, 2H), 7.38 (t, 1H, J=7.9 Hz), 7.23 (d, 1H, J=7.7 Hz), 7.19 (d, 1H, J=1.9 Hz), 7.02 (d, 1H, J=8.2 Hz), 6.94 (dd, 1H, J=8.2, 2.4 Hz), 3.88 (s, 3H), 1.98 (s, 3H), 19F-NMR (DMSO-d6) δ −81.88 (s, 1F), Anal. Calc. For C17H14F3NO3: C, 60.54; H, 4.18; N, 4.15. Found: C, 60.58; H, 4.44; N, 4.19.

Workup

  1. customto remove oxygen
  2. temperaturethe reaction solution was heated at 95° C. under nitrogen for 48 hours
  3. temperatureThe reaction solution was cooled to room temperature
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×20 mL)
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. customAfter removal of solvent
  9. customthe residue was purified by a flash chromatography (silica gel, hexane:ethyl acetate/4:1)

Sources & evidence

ORD record
ord-5f39f6a6ef3143a5934a1327ca6ccb87
Source dataset
uspto-grants-2004_03
Patent number
US06713478B2

Reaction notes

Loading…