Water → 8-benzyl-3-[(1R)-1-cyclopropylethoxy]-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

HRID 2188641Notes

Reaction equation

HRID 2188641 reaction equation
[CH:1]1([C@H:4]([OH:6])[CH3:5])[CH2:3][CH2:2]1.[H-].[Na+].[CH2:9]([N:16]1[CH2:22][C:21]2[N:23]=[CH:24][C:25](Cl)=[N:26][C:20]=2[O:19][CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.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].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>[CH2:9]([N:16]1[CH2:22][C:21]2[N:23]=[CH:24][C:25]([O:6][C@@H:4]([CH:1]3[CH2:3][CH2:2]3)[CH3:5])=[N:26][C:20]=2[O:19][CH2:18][CH2:17]1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 6999829(1R)-1-cyclopropylethan-1-olHCID 866489818-Benzyl-3-chloro-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

Product 1

HCID 669931558-benzyl-3-[(1R)-1-cyclopropylethoxy]-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepineYield 67.2%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×

Procedure

To a solution of (1R)-1-cyclopropylethanol (130 mg) in toluene (3 mL) was added sodium hydride (120 mg), and the mixture was stirred under a nitrogen atmosphere at room temperature for 15 min. A mixture of 8-benzyl-3-chloro-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine (415 mg), BINAP (41 mg), Pd2(dba)3 (28 mg) and toluene (3 mL) was added, and the mixture was stirred under an argon atmosphere at 100° C. for 3 hr. Water was added to the reaction solution, and the resultant product 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 (329 mg, 67%) as a yellow oil.

Workup

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

Sources & evidence

ORD record
ord-d0fd7c17a73b43cbbab45a2554898073
Source dataset
uspto-grants-2012_12
Patent number
US08324201B2

Reaction notes

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