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

HRID 5386

Reaction equation

HRID 5386 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-805756e25c6e47c98a7e9f3b4a6eca54
Source dataset
uspto-grants-1993_09
Patent number
US05244907

Linked notes

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