Isopropanol → 8-Benzyl-3-(1-methylethoxy)-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

HRID 2188640Notes

Reaction equation

HRID 2188640 reaction equation
[CH:1]([OH:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:7]([N:14]1[CH2:20][C:19]2[N:21]=[CH:22][C:23](Cl)=[N:24][C:18]=2[O:17][CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=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].O>[CH2:7]([N:14]1[CH2:20][C:19]2[N:21]=[CH:22][C:23]([O:4][CH:1]([CH3:3])[CH3:2])=[N:24][C:18]=2[O:17][CH2:16][CH2:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 24758Sodium hydrideHCID 634876Binap, (A+-)-HCID 866489818-Benzyl-3-chloro-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

Product 1

HCID 669936768-Benzyl-3-(1-methylethoxy)-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepineYield 42%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

To a solution of isopropanol (83 μL) in toluene (2 mL) was added sodium hydride (87 mg) at room temperature, and the mixture was stirred for 15 min. A solution of 8-benzyl-3-chloro-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine (297 mg) and BINAP (30 mg) in toluene (2 mL) was added to the reaction mixture. After substitution with an argon gas, Pd2(dba)3 (20 mg) was added, and the mixture was stirred under an argon atmosphere at 100° C. for 1 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried, and the solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (solvent gradient; 5→50% ethyl acetate/hexane) to give the title compound (137 mg, 42%) as a colorless oil.

Workup

  1. stirringthe mixture was stirred under an argon atmosphere at 100° C. for 1 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine
  4. customdried
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (solvent gradient; 5→50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-008369f95b5b4b2c90888be4b5c059be
Source dataset
uspto-grants-2012_12
Patent number
US08324201B2

Reaction notes

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