Reacción #5481

Ecuación de reacción

n-butyllithium hexane

1-azabicyclo[3.3.1]nonane-5-methanol

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

1,1'-carbonyldiimidazole

→

pale yellow solid

Rendimiento 57.3%

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

Rendimiento 57.3%

Disolventes

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrodegassed with a stream of nitrogen over 10 minutes
2. 2
   workup.STIRRINGstirred for 30 minutes
3. 3
   Concentraciónconcentrated in vacuo
4. 4
   OtroThe above prepared suspension
5. 5
   workup.STIRRINGthe mixture was stirred overnight (18 hours)
6. 6
   Concentraciónconcentrated in vacuo
7. 7
   OtroThe 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
   Otrothe organic layer was separated
10. 10
    ExtracciónThe aqueous solution was extracted with methylene chloride (2×50 mL)
11. 11
    Secadothe combined organic solution was dried (Na2SO4)
12. 12
    Concentraciónconcentrated in vacuo
13. 13
    Otrorecrystallized from acetonitrile (2 crops)

Procedimiento

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.

Fuente