تفاعل #5481

معادلة التفاعل

n-butyllithium hexane

1-azabicyclo[3.3.1]nonane-5-methanol

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

1,1'-carbonyldiimidazole

→

pale yellow solid

المردود 57.3%

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

المردود 57.3%

المذيبات

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىdegassed with a stream of nitrogen over 10 minutes
2. 2
   workup.STIRRINGstirred for 30 minutes
3. 3
   تركيزconcentrated in vacuo
4. 4
   أخرىThe above prepared suspension
5. 5
   workup.STIRRINGthe mixture was stirred overnight (18 hours)
6. 6
   تركيزconcentrated in vacuo
7. 7
   أخرىThe 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
   أخرىthe organic layer was separated
10. 10
    استخلاصThe aqueous solution was extracted with methylene chloride (2×50 mL)
11. 11
    تجفيفthe combined organic solution was dried (Na2SO4)
12. 12
    تركيزconcentrated in vacuo
13. 13
    أخرىrecrystallized from acetonitrile (2 crops)

الإجراء التجريبي

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.

المصدر