Binap, (A+-)- → ethyl (3R)-3-methyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate

HRID 516255Notes

Reaction equation

HRID 516255 reaction equation
[NH2:1][C@H:2]([CH3:22])[CH2:3][O:4][C:5]1[C:20](Br)=[CH:19][C:8]2[CH2:9][CH2:10][N:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12][CH2:13][C:7]=2[CH:6]=1.CC(C)([O-])C.[Na+].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>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]>[CH3:22][C@@H:2]1[CH2:3][O:4][C:5]2[C:20](=[CH:19][C:8]3[CH2:9][CH2:10][N:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12][CH2:13][C:7]=3[CH:6]=2)[NH:1]1

Participants

6

Reactant 3

HCID 634876Binap, (A+-)-2×HCID 23676156Sodium t-butoxide2×HCID 58495302HCID 58495302, compound

Product 1

HCID 66982702ethyl (3R)-3-methyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylateYield 47.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Under an argon atmosphere, to a solution of 1.64 g of ethyl 7-{[(2R)-2-aminopropyl]oxy}-8-bromo-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate in 41 ml of toluene were added 509 mg of sodium t-butoxide, 275 mg of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, and 202 mg of tris(dibenzylideneacetone)dipalladium (0) in this order, followed by heating at 100° C. for 24 hours. Further, 509 mg of sodium t-butoxide, 275 mg of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, and 202 mg of tris(dibenzylideneacetone)dipalladium (0) were added thereto, followed by stirring at 100° C. for additional 24 hours. The reaction mixture was returned to room temperature, then filtered through celite, and washed with ethyl acetate, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: Hex-AcOEt) to obtain 610 mg of ethyl (3R)-3-methyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate.

Workup

  1. customwas returned to room temperature
  2. filtrationfiltered through celite
  3. washwashed with ethyl acetate
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (elution solvent: Hex-AcOEt)

Sources & evidence

ORD record
ord-f5566578c8604758814880f0bff960dc
Source dataset
uspto-grants-2015_08
Patent number
US09108977B2

Reaction notes

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