Reaction #5482

Reaction equation

n-butyllithium hexane

1-azabicyclo[3.3.1]nonane-5-methanol

indole-3-carboxylic acid

1,1'-carbonyldiimidazole

→

colorless crystals

Yield 60.0%

1H-Indole-3-carboxylic acid 1-azabicyclo[3.3.1]non-5-ylmethyl ester

Yield 60.0%

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Otherdegassed with a stream of nitrogen for 10 minutes
2. 2
   Othergiving a suspension
3. 3
   workup.STIRRINGstirred for 30 minutes
4. 4
   Concentrationconcentrated in vacuo
5. 5
   workup.STIRRINGthe mixture was stirred overnight (18 hours)
6. 6
   Concentrationconcentrated in vacuo
7. 7
   OtherThe residue was partitioned between methylene chloride (100 mL)
8. 8
   workup.ADDITIONcontaining a little isopropanol and saturated sodium carbonate (50 mL)
9. 9
   Otherthe organic layer was separated
10. 10
    DryingThe aqueous solution was dried (Na2SO4)
11. 11
    Concentrationconcentrated in vacuo
12. 12
    Filtrationfiltered through alumina (eluted with 7% methanol/methylene chloride)
13. 13
    ConcentrationThe filtrated was concentrated in vacuo
14. 14
    Otherthe residue was triturated from cold ether
15. 15
    Otherrecrystallized from acetonitrile (2 crops)

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.

Source