1,1'-Carbonyldiimidazole → 1H-Indole-3-carboxylic acid 1-azabicyclo[3.3.1]non-5-ylmethyl ester

HRID 5386

反応式

HRID 5386 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=[O:11])=[CH:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[N:25]12[CH2:33][C:29]([CH2:34]O)([CH2:30][CH2:31][CH2:32]1)[CH2:28][CH2:27][CH2:26]2.C([Li])CCC.CCCCCC>O1CCCC1>[N:25]12[CH2:33][C:29]([CH2:34][O:11][C:10]([C:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[NH:1][CH:2]=3)=[O:12])([CH2:30][CH2:31][CH2:32]1)[CH2:28][CH2:27][CH2:26]2

参加物

6

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 69867Indole-3-Carboxylic AcidHCID 19795980{1-Azabicyclo[3.3.1]nonan-5-yl}methanolHCID 178418244HCID 178418244、化合物

生成物 1

HCID 541492491H-Indole-3-carboxylic acid 1-azabicyclo[3.3.1]non-5-ylmethyl ester収率 60%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of indole-3-carboxylic acid (1.62 g, 10 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.70 g, 10.5 mmol), stirred for one hour, and degassed with a stream of nitrogen for 10 minutes giving a suspension. Meanwhile, a cooled (-10° C.) solution of 1-azabicyclo[3.3.1]nonane-5-methanol (1.71 g, 11 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated (via syringe) with 2.5N n-butyllithium/hexane (10.7 mmol), stirred for 30 minutes, concentrated in vacuo, and taken up in anhydrous tetrahydrofuran (10 mL) under nitrogen. The 1,1'-carbonyldiimidazole adduct suspension was transferred into this solution, and the mixture was stirred overnight (18 hours) and concentrated in vacuo. The residue was partitioned between methylene chloride (100 mL) containing a little isopropanol and saturated sodium carbonate (50 mL), and the organic layer was separated. The aqueous solution was dried (Na2SO4), concentrated in vacuo, and filtered through alumina (eluted with 7% methanol/methylene chloride). The filtrated was concentrated in vacuo and the residue was triturated from cold ether and recrystallized from acetonitrile (2 crops) to afford 1.79 g (60%) of colorless crystals; m.p. 207°-209° C.

後処理

  1. customdegassed with a stream of nitrogen for 10 minutes
  2. customgiving a suspension
  3. stirringstirred for 30 minutes
  4. concentrationconcentrated in vacuo
  5. stirringthe mixture was stirred overnight (18 hours)
  6. concentrationconcentrated in vacuo
  7. customThe residue was partitioned between methylene chloride (100 mL)
  8. additioncontaining a little isopropanol and saturated sodium carbonate (50 mL)
  9. customthe organic layer was separated
  10. dry with materialThe aqueous solution was dried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. filtrationfiltered through alumina (eluted with 7% methanol/methylene chloride)
  13. concentrationThe filtrated was concentrated in vacuo
  14. customthe residue was triturated from cold ether
  15. customrecrystallized from acetonitrile (2 crops)

出典と根拠

ORDレコード
ord-805756e25c6e47c98a7e9f3b4a6eca54
出典データセット
uspto-grants-1993_09
特許番号
US05244907

関連ノート

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