4-(2-Oxiranylmethoxy)benzenecarbonitrile → 4-{3-[(3-Benzyl-3-azabicyclo[3.2.1]oct-8-yl)(methyl)amino]-2-hydroxypropoxy}benzonitrile

HRID 411519노트

반응식

HRID 411519 반응식
[CH2:1]([N:8]1[CH2:14][CH:13]2[CH:15]([NH:16][CH3:17])[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Al](C)C.[O:22]1[CH2:24][CH:23]1[CH2:25][O:26][C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=1>ClCCl>[CH2:1]([N:8]1[CH2:14][CH:13]2[CH:15]([N:16]([CH3:17])[CH2:24][CH:23]([OH:22])[CH2:25][O:26][C:27]3[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=3)[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 3

HCID 27643014-(2-Oxiranylmethoxy)benzenecarbonitrileHCID 16682925TrimethylaluminumHCID 185410303-benzyl-N-methyl-3-azabicyclo[3.2.1]octan-8-amine

생성물 1

HCID 185408994-{3-[(3-Benzyl-3-azabicyclo[3.2.1]oct-8-yl)(methyl)amino]-2-hydroxypropoxy}benzonitrile수율 66%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
25 °C

실험 절차

To a solution of 3-benzyl-N-methyl-3-azabicyclo[3.2.1]octan-8-amine (Preparation B; 3.72 g, 16.1 mmol) in dichloromethane (80 mL) at 25° C. under nitrogen was added trimethylaluminum (8.05 mL of 2.0 M in hexane, 16.1 mmol). After stirring at 25° C. for 30 min, 4-(2-oxiranyl-methoxy)benzonitrile (see step (i) above; 2.83 g, 16.1 mmol) was added in one portion, and the mixture was stirred overnight. The mixture was quenched with 6 N NaOH (13.5 mL) and stirred 1 h. Water (100 mL) was added, and the aqueous layer was extracted with dichloromethane (3×100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford an oil. The residue was chromatographed on silica gel, eluting with dichloromethane:methanol (98:2), to afford 4.30 g (66%) of the sub-title compound as a colorless oil.

후처리

  1. stirringthe mixture was stirred overnight
  2. customThe mixture was quenched with 6 N NaOH (13.5 mL)
  3. stirringstirred 1 h
  4. additionWater (100 mL) was added
  5. extractionthe aqueous layer was extracted with dichloromethane (3×100 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford an oil
  10. customThe residue was chromatographed on silica gel
  11. washeluting with dichloromethane:methanol (98:2)

출처 및 근거

ORD 기록
ord-da50a9c901144305afed45d238547caa
출처 데이터셋
uspto-grants-2003_05
특허 번호
US06559162B2

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