Ethyl Acetate → 2-Bromo-6-(8-tert-butyl-5-oxo-2,3-dihydro-5H-benzo[f][1,4]oxazepin-4-yl)benzaldehyde

HRID 1879679Notes

Reaction equation

HRID 1879679 reaction equation
[C:1]([C:5]1[CH:16]=[CH:15][C:8]2[C:9](=[O:14])[NH:10][CH2:11][CH2:12][O:13][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Br:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22](Br)[C:19]=1[CH:20]=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.O>[Br:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22]([N:10]2[C:9](=[O:14])[C:8]3[CH:15]=[CH:16][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:6][C:7]=3[O:13][CH2:12][CH2:11]2)[C:19]=1[CH:20]=[O:21]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 126486412,6-DibromobenzaldehydeHCID 595485458-tert-Butyl-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one

Product 1

HCID 595485352-Bromo-6-(8-tert-butyl-5-oxo-2,3-dihydro-5H-benzo[f][1,4]oxazepin-4-yl)benzaldehyde

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

8-tert-Butyl-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one (600 mg, 2.74 mmol, 2,6-Dibromo-benzaldehyde (3.62 g, 5eq), Xanthphos (71 mg, 0.045eq), and cesium carbonate (1.25 g, 1.4 eq) were taken up in dioxane (5.3 mL) and a stream of Argon gas was bubbled through the mixture for 10 minutes. The catalyst Pd(dba)2 (47 mg, 0.03 eq) was added and the resulting mixture was placed under argon and stirred at 100° C. for three hours. By TLC, the reaction was complete and after cooling the mixture to room temperature, ethyl acetate (150 mL) and water (50 mL) were added and the layers were partitioned and separated. The organic layer was further washed with water (3×50 mL) and finally washed with brine (1×50 mL) before it was dried over magnesium sulfate, filtered and concentrated. Purification by column chromatography on silica gel eluting with a gradient of 5% ethyl acetate to 30% ethyl acetate afforded the title compound as an off-white powder (793 mg) (M+H)+=404.

Workup

  1. customa stream of Argon gas was bubbled through the mixture for 10 minutes
  2. temperatureafter cooling the mixture to room temperature
  3. customthe layers were partitioned
  4. customseparated
  5. washThe organic layer was further washed with water (3×50 mL)
  6. washfinally washed with brine (1×50 mL) before it
  7. dry with materialwas dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by column chromatography on silica gel eluting with a gradient of 5% ethyl acetate to 30% ethyl acetate

Sources & evidence

ORD record
ord-526df6a040d44c0f8346d26455f1fd64
Source dataset
uspto-grants-2012_11
Patent number
US08318719B2

Reaction notes

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