Bromobenzene → Ethyl 3,4-dihydro-4-phenyl-2H-1,4-benzoxazine-2-carboxylate

HRID 1696294Notes

Reaction equation

HRID 1696294 reaction equation
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.Br[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.[O:50]1[CH:55]([C:56]([O:58][CH2:59][CH3:60])=[O:57])[CH2:54][NH:53][C:52]2[CH:61]=[CH:62][CH:63]=[CH:64][C:51]1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:44]1([N:53]2[CH2:54][CH:55]([C:56]([O:58][CH2:59][CH3:60])=[O:57])[O:50][C:51]3[CH:64]=[CH:63][CH:62]=[CH:61][C:52]2=3)[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

8

Reactant 4

HCID 7961BromobenzeneHCID 10796Cesium carbonateHCID 31090Ethyl 3,4-dihydro-2H-1,4-benzoxazine-2-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)

Product 1

HCID 86614014Ethyl 3,4-dihydro-4-phenyl-2H-1,4-benzoxazine-2-carboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Tris(dibenzylideneacetone)dipalladium (0) (4.3 mg, 0.0046 mmol), xantphos (8.2 mg, 0.014 mmol), and bromobenzene (40 L, 0.381 mmol) were added to a solution of (±)-ethyl 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate (65 mg, 0.31 mmol) in dioxane (2.5 mL). The solids were allowed to dissolve, and cesium carbonate (143 mg, 0.44 mmol) was added, and the suspension was stirred at 100° C. for 24 h. The mixture was cooled to ambient temperature, diluted with water (20 mL), and the product was extracted with 67% EtOAc/hexane (3×25 mL). The organic layers were combined, dried over sodium sulfate, and concentrated. Purification of the crude concentrate by flash column chromatography using 15% EtOAc/hexane afforded the title compound. MS m/z: 284 (M+1).

Workup

  1. dissolutionto dissolve
  2. temperatureThe mixture was cooled to ambient temperature
  3. extractionthe product was extracted with 67% EtOAc/hexane (3×25 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customPurification of the crude
  7. concentrationconcentrate by flash column chromatography

Sources & evidence

ORD record
ord-27473953a74f43f2816a5b7d41d3c917
Source dataset
uspto-grants-2012_04
Patent number
US08163766B2

Reaction notes

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