4-(2-Oxiranylmethoxy)benzenecarbonitrile → Tert-butyl 3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3-azabicyclo-[3.2.1]oct-8-yl(methyl)carbamate

HRID 411520ノート

反応式

HRID 411520 の反応式
[CH:1]12[CH:8]([N:9]([CH3:17])[C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:5]([CH2:6][CH2:7]1)[CH2:4][NH:3][CH2:2]2.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>[C:31]([C:30]1[CH:33]=[CH:34][C:27]([O:26][CH2:25][CH:23]([OH:22])[CH2:24][N:3]2[CH2:4][CH:5]3[CH:8]([N:9]([CH3:17])[C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:14])[CH3:15])[CH:1]([CH2:7][CH2:6]3)[CH2:2]2)=[CH:28][CH:29]=1)#[N:32]

参加物

5

反応物 3

HCID 27643014-(2-Oxiranylmethoxy)benzenecarbonitrileHCID 16682925TrimethylaluminumHCID 18541001Tert-butyl 3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate

生成物 1

HCID 18540975Tert-butyl 3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3-azabicyclo-[3.2.1]oct-8-yl(methyl)carbamate収率 81%

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 tert-butyl 3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate (Preparation D; 1.68 g, 7.0 mmol) in dichloromethane (35 mL) at 25° C. under nitrogen was added trimethylaluminum (3.75 mL of 2.0 M in hexanes, 7.0 mmol). After stirring at 25° C. for 30 min, 4-(2-oxiranyl-methoxy)benzonitrile (Preparation E(i); 1.22 g, 7.0 mmol) was added in one portion, and the mixture was stirred overnight. The mixture was quenched with 3 N NaOH (11.5 mL) and stirred for 1 h. Water (30 mL) was added, and the aqueous layer was extracted with dichloromethane (3×30 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 2.35 g (81%) of the subtitle compound as a white solid.

後処理

  1. stirringthe mixture was stirred overnight
  2. customThe mixture was quenched with 3 N NaOH (11.5 mL)
  3. stirringstirred for 1 h
  4. additionWater (30 mL) was added
  5. extractionthe aqueous layer was extracted with dichloromethane (3×30 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-46ed3642345845818ef5a4267015ecac
出典データセット
uspto-grants-2003_05
特許番号
US06559162B2

反応ノート

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