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Morpholine → (6S)-8-benzyl-6-methyl-3-(morpholin-4-yl)-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

HRID 1879698
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HRID 1879698 반응식
[CH2:1]([N:8]1[CH2:14][C:13]2[N:15]=[CH:16][C:17](Cl)=[N:18][C:12]=2[O:11][C@@H:10]([CH3:20])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>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>[CH2:1]([N:8]1[CH2:14][C:13]2[N:15]=[CH:16][C:17]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[N:18][C:12]=2[O:11][C@@H:10]([CH3:20])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
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참가 물질

8

반응물 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 86648983(6S)-8-benzyl-3-chloro-6-methyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

생성물 1

HCID 66993586(6S)-8-benzyl-6-methyl-3-(morpholin-4-yl)-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine수율 20%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매

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온도
100 °C

실험 절차

A suspension of (6S)-8-benzyl-3-chloro-6-methyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine (301 mg), morpholine (0.11 mL), Pd2(dba)3 (19 mg), XPhos (40 mg) and sodium tert-butoxide (250 mg) in toluene (5 mL) was stirred under an argon atmosphere with heating at 100° C. for 2 hr. Water was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (solvent gradient: 9→50% ethyl acetate/hexane) to give the title compound (70 mg, 20%) as a colorless oil.

후처리

  1. extractionthe aqueous layer was extracted with ethyl acetate
  2. washthe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (solvent gradient: 9→50% ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-76fc71efad5a492d886a3feceadb36be
출처 데이터셋
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08318722B2

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