Dimethylformamide → 4-(2-methoxy-4-(trifluoromethyl)phenyl)-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one

HRID 528638Notes

Reaction equation

HRID 528638 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:15]=1[OH:23].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C.Cl[CH2:36][C:37](Cl)=[O:38]>CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[N:13]1[C:37](=[O:38])[CH2:36][O:23][C:15]2[CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=[CH:19][C:14]1=2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6577Chloroacetyl chlorideHCID 10796Cesium carbonateHCID 897612612-((2-Methoxy-4-(trifluoromethyl)phenyl)amino)-5-nitrophenol

Product 1

HCID 897619994-(2-methoxy-4-(trifluoromethyl)phenyl)-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-oneYield 107%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a flask charged with 2-((2-methoxy-4-(trifluoromethyl)phenyl)amino)-5-nitrophenol (1.75 g, 5.33 mmol) and cesium carbonate (8.69 g, 26.7 mmol) was added DMF (21.33 ml) followed by chloroacetyl chloride (0.854 ml, 10.66 mmol), dropwise over 5 min. The resulting solution was maintained at rt for 1 h. Quenched reaction with saturated ammonium chloride (25 mL) and diluted with EtOAc (25 mL). Separated layers, and extracted aqueous layer with EtOAc (3×25 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated via rotary evaporation to provide 4-(2-methoxy-4-(trifluoromethyl)phenyl)-7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one (2.10 g, 5.70 mmol, 107% yield) as a yellow solid. The crude product was used in the next step without further purification.

Workup

  1. customQuenched
  2. customreaction with saturated ammonium chloride (25 mL)
  3. extractionSeparated layers, and extracted aqueous layer with EtOAc (3×25 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated via rotary evaporation

Sources & evidence

ORD record
ord-56506c9d8ad346ddb675c3f937d435a2
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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