Reacción #5473

Ecuación de reacción

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

1,1'-carbonyldiimidazole

1-azabicyclo[3.2.1]octane-5-methanamine

→

colorless crystals

Rendimiento 70.0%

4-Amino-N-(1-azabicyclo[3.2.1]oct-5ylmethyl)-5-chloro-2-methoxybenzamide

Rendimiento 70.0%

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrodegassed under a stream of nitrogen for 10 minutes
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITwas continued at room temperature for 18 hours and at 50° C. for one hour
4. 4
   ConcentraciónThe mixture was concentrated in vacuo
5. 5
   Otropartitioned between toluene (100 mL)
6. 6
   workup.ADDITIONcontaining a little 2-propanol and saturated sodium carbonate (50 mL)
7. 7
   OtroThe organic layer was separated
8. 8
   Secadothe organic solution was dried (Na2SO4)
9. 9
   Concentraciónconcentrated in vacuo
10. 10
    Otrotriturated from cold ether
11. 11
    OtroRecrystallization from acetonitrile (2 crops)

Procedimiento

A suspension of 4-amino-5-chloro-2-methoxybenzoic acid (1.72 g, 8.5 mmol) in anhydrous tetrahydrofuan (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.46 g, 9.0 mmol), stirred for one hour, then degassed under a stream of nitrogen for 10 minutes. A solution of 1-azabicyclo[3.2.1]octane-5-methanamine (1.27 g, 9.0 mmol) in anhydrous tetrahydrofuran (8 mL) was added, and stirring was continued at room temperature for 18 hours and at 50° C. for one hour. The mixture was concentrated in vacuo and partitioned between toluene (100 mL) containing a little 2-propanol and saturated sodium carbonate (50 mL). The organic layer was separated and the organic solution was dried (Na2SO4), concentrated in vacuo, and triturated from cold ether. Recrystallization from acetonitrile (2 crops) afforded 1.92 g (70%) of colorless crystals; mp 185°-187° C.

Fuente