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

HRID 411519ノート

反応式

HRID 411519 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-da50a9c901144305afed45d238547caa
出典データセット
uspto-grants-2003_05
特許番号
US06559162B2

反応ノート

読み込み中…