反応 #5479

反応方程式

n-butyllithium hexane

1-azabicyclo[3.2.1]octane-5-methanol

indole-3-carboxylic acid

1,1'-carbonyldiimidazole

→

colorless solid

収率 52.4%

1H-Indole-3-carboxylic acid 1-azabicyclo[3.2.1]oct-5-ylmethyl ester

収率 52.4%

溶媒

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   その他degassed with a stream of nitrogen over 10 minutes
2. 2
   workup.STIRRINGstirred for 30 minutes
3. 3
   濃縮concentrated in vacuo
4. 4
   workup.STIRRINGthe mixture was stirred overnight (18 hours)
5. 5
   濃縮concentrated in vacuo
6. 6
   その他The residue was partitioned between methylene chloride (100 mL)
7. 7
   workup.ADDITIONcontaining a little 2-propanol and saturated aqueous sodium carbonate (50 mL)
8. 8
   その他the organic layer was separated
9. 9
   抽出The aqueous solution was extracted with methylene chloride (2×50 mL)
10. 10
    乾燥the combined organic solution was dried (Na2SO4)
11. 11
    濃縮concentrated in vacuo
12. 12
    ろ過filtered through alumina (eluted with 5% methanol/methylene chloride)
13. 13
    その他The concentrated filtrate was recrystallized from acetonitrile (2 crops)

実験手順

A solution of indole-3-carboxylic acid (1.45 g, 9 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.53 g, 9.4 mmol), stirred for one hour, and degassed with a stream of nitrogen over 10 minutes. Meanwhile, a cooled (-10° C.) solution of 1-azabicyclo[3.2.1]octane-5-methanol (1.42 g, 10 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated (via syringe) with 2.5N n-butyllithium/hexane (9.7 mmol), stirred for 30 minutes, concentrated in vacuo, and taken up in anhydrous tetrahydrofuran (10 mL) under nitrogen. The acid 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 2-propanol and saturated aqueous sodium carbonate (50 mL), and the organic layer was separated. The aqueous solution was extracted with methylene chloride (2×50 mL), and the combined organic solution was dried (Na2SO4), concentrated in vacuo, and filtered through alumina (eluted with 5% methanol/methylene chloride). The concentrated filtrate was recrystallized from acetonitrile (2 crops) to afford 1.34 g (52%) of colorless solid; mp 183.5°-185.0° C.

出典