반응 #5481

반응 방정식

n-butyllithium hexane

1-azabicyclo[3.3.1]nonane-5-methanol

4-amino-5-chloro-2-methoxybenzoic acid

1,1'-carbonyldiimidazole

→

pale yellow solid

수율 57.3%

4-Amino-5-chloro-2-methoxybenzoic acid 1-azabicyclo[3.3.1]non-5-ylmethyl ester

수율 57.3%

용매

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   기타degassed with a stream of nitrogen over 10 minutes
2. 2
   workup.STIRRINGstirred for 30 minutes
3. 3
   농축concentrated in vacuo
4. 4
   기타The above prepared suspension
5. 5
   workup.STIRRINGthe mixture was stirred overnight (18 hours)
6. 6
   농축concentrated in vacuo
7. 7
   기타The residue was partitioned between methylene chloride (100 mL)
8. 8
   workup.ADDITIONcontaining a little 2-propanol and saturated aqueous sodium carbonate (50 mL)
9. 9
   기타the organic layer was separated
10. 10
    추출The aqueous solution was extracted with methylene chloride (2×50 mL)
11. 11
    건조the combined organic solution was dried (Na2SO4)
12. 12
    농축concentrated in vacuo
13. 13
    기타recrystallized from acetonitrile (2 crops)

실험 절차

A solution of 4-amino-5-chloro-2-methoxybenzoic acid (2.02 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, then degassed with a stream of nitrogen over 10 minutes. 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 above prepared 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 recrystallized from acetonitrile (2 crops) to afford 1.94 g (57%) of pale yellow solid; mp 152.5°-154.5° C.

출처