Methanol → HCID 66790291, compound

HRID 1929436Notes

Reaction equation

HRID 1929436 reaction equation
Cl[C:2]1[C:3]([N+:22]([O-:24])=[O:23])=[CH:4][C:5]2[O:10][C:9]([CH3:12])([CH3:11])[C:8](=[O:13])[N:7]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[C:6]=2[CH:21]=1.[C:25](=O)([O-])[O-:26].[Cs+].[Cs+].CO.C1(C)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.O>[F:20][C:17]1[CH:18]=[CH:19][C:14]([N:7]2[C:6]3[CH:21]=[C:2]([O:26][CH3:25])[C:3]([N+:22]([O-:24])=[O:23])=[CH:4][C:5]=3[O:10][C:9]([CH3:12])([CH3:11])[C:8]2=[O:13])=[CH:15][CH:16]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 1140TolueneHCID 10796Cesium carbonateHCID 66790552HCID 66790552, compound

Product 1

HCID 66790291HCID 66790291, compoundYield 37.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineCatalystHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 6-chloro-4-(4-fluorophenyl)-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-3(4H)-one (compound obtained in Reference Example 50(2); 400 mg), palladium acetate (5.1 mg), racemic 2-(di-tert-butylphosphino)-1,1′-binaphthyl (11.4 mg), cesium carbonate (557 mg), methanol (1 mL) and toluene (4 mL) was stirred at 70° C. under argon atmosphere for 26 hours. After cooling, to the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The resultant residue was suspended in chloroform (4 mL) and thereto was added 1-hydroxybenzotriazole (154 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (208 mg). The mixture was stirred at room temperature for 3 hours. To the reaction mixture was added water, and the mixture was extracted with chloroform. The organic layer was washed successively with an aqueous saturated sodium hydrogencarbonate solution and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on NH-silica gel (Chromatorex NH-silica gel; solvent; n-hexane/ethyl acetate=9/1) to give 4-(4-fluorophenyl)-6-methoxy-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-3(4H)-one (147 mg) as a pale yellow powder.

Workup

  1. temperatureAfter cooling, to the reaction mixture
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. additionwas added 1-hydroxybenzotriazole (154 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (208 mg)
  7. stirringThe mixture was stirred at room temperature for 3 hours
  8. additionTo the reaction mixture was added water
  9. extractionthe mixture was extracted with chloroform
  10. washThe organic layer was washed successively with an aqueous saturated sodium hydrogencarbonate solution and brine
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by column chromatography on NH-silica gel (Chromatorex NH-silica gel; solvent; n-hexane/ethyl acetate=9/1)

Sources & evidence

ORD record
ord-f2ff74d3437d4c388ad78730ba31637d
Source dataset
uspto-grants-2012_05
Patent number
US08188073B2

Reaction notes

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