反应详情

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.

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)