반응 #5483

반응 방정식

1-azabicyclo[3.2.1]oct-5-ylmethanol

n-butyllithium hexane

3-(3H-imidazol-1-ylcarbonyl)-1-methyl-1H-indazole

→

product

수율 53.1%

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

수율 53.1%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   농축concentrated in vacuo
2. 2
   기타to remove all hexane
3. 3
   workup.ADDITIONAnhydrous tetrahydrofuran (15 mL) was added
4. 4
   workup.STIRRINGthe mixture was stirred under nitrogen at room temperature for 18 hours
5. 5
   농축concentrated in vacuo
6. 6
   기타The residue was partitioned between 1.0N sodium carbonate (75 mL) and toluene (125 mL)
7. 7
   workup.ADDITIONcontaining some 2-propanol
8. 8
   추출The aqueous solution was extracted with toluene (2×50 mL)
9. 9
   workup.ADDITIONcontaining some 2-propanol
10. 10
    세척the combined organic solution was rinsed with water
11. 11
    기타to remove imidazole
12. 12
    건조dried azeotropically with toluene
13. 13
    여과The residue was filtered through alumina (eluted with 15% methanol/tetrahydrofuran)
14. 14
    농축concentrated in vacuo
15. 15
    기타triturated from ether/petroleum ethers (30°-60°)
16. 16
    기타recrystallized from ether/petroleum ethers (30°-60°)

실험 절차

A cooled (0° C.) solution of 1-azabicyclo[3.2.1]oct-5-ylmethanol (1.70 g, 12 mmol) in anhydrous tetrahydrofuran (15 mL) under nitrogen was treated (via syringe) with 2.45N n-butyllithium/hexane (12 mmol), then stirred at room temperature for thirty minutes and concentrated in vacuo to remove all hexane. Anhydrous tetrahydrofuran (15 mL) was added, followed by 3-(3H-imidazol-1-ylcarbonyl)-1-methyl-1H-indazole (2.49 g, 11 mmol), and the mixture was stirred under nitrogen at room temperature for 18 hours, then at 60° C. for three hours, and concentrated in vacuo. The residue was partitioned between 1.0N sodium carbonate (75 mL) and toluene (125 mL) containing some 2-propanol, and the organic layer was set aside. The aqueous solution was extracted with toluene (2×50 mL) containing some 2-propanol, and the combined organic solution was rinsed with water to remove imidazole, then dried azeotropically with toluene. The residue was filtered through alumina (eluted with 15% methanol/tetrahydrofuran), concentrated in vacuo, and triturated from ether/petroleum ethers (30°-60°), then recrystallized from ether/petroleum ethers (30°-60°) to afford 1.75 g (53%) of the product as a colorless solid; mp 93°-95° C.

출처