Water → (R)-7-benzyloxy-3-(4-benzyloxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazine

HRID 460461Notes

Reaction equation

HRID 460461 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12](Br)=[C:13]([CH:32]=1)[O:14][CH2:15][C@H:16]([NH2:31])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[K+].O>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.CCCCCC>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[NH:31][C@H:16]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:19][CH:18]=3)[CH2:15][O:14][C:13]=2[CH:32]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 60086312(R)-2-(5-benzyloxy-2-bromophenoxy)-1-(4-benzyloxyphenyl)ethylamine

Product 1

HCID 20726824(R)-7-benzyloxy-3-(4-benzyloxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazineYield 55%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

A solution of (R)-2-(5-benzyloxy-2-bromophenoxy)-1-(4-benzyloxyphenyl)ethylamine (120 mg, 0.238 mmol), tris(dibenzylideneacetone)dipalladium (11 mg, 0.012 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (15 mg, 0.024 mmol) and potassium-t-butoxide (37 mg, 0.330 mmol) in toluene (2.5 ml) was stirred for 3 hours at 100° C. under a nitrogen stream. After cooling, water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/5, v/v) to give (R)-7-benzyloxy-3-(4-benzyloxy-phenyl)-3,4-dihydro-2H-benzo[1,4]oxazine (55.4 mg, Yield 55%).

Workup

  1. temperatureAfter cooling
  2. extractionwas then extracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-2389875375fb4571a49f6c19654818a2
Source dataset
uspto-grants-2007_03
Patent number
US07196081B2

Reaction notes

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