Reacción #5474

Ecuación de reacción

1-azabicyclo[3.3.1]nonane-5-methanamine

5-chloro-2-methoxy-4-(methylamino)benzoic acid

1,1'-carbonyldiimidazole

→

colorless crystals

Rendimiento 73.3%

N-(1-Azabicyclo[3.3.1]non-5-ylmethyl)-5-chloro-2-methoxy-4-(methylamino)benzamide

Rendimiento 73.3%

Disolventes

tetrahydrofuran

methanol

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
4. 4
   workup.DISSOLUTIONto dissolve the solid
5. 5
   Filtraciónthe solution was filtered through a short column of alumina (eluted with 20% methanol/tetrahydrofuran)
6. 6
   ConcentraciónThe filtrate was concentrated in vacuo
7. 7
   Otrotriturated from cold ether
8. 8
   Otrorecrystallized from acetonitrile

Procedimiento

A solution of 5-chloro-2-methoxy-4-(methylamino)benzoic acid (1.08 g, 5 mmol) in anhydrous tetrahydrofuran (7 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (0.90 g, 5.5 mmol), stirred one hour, degassed under a stream of nitrogen for 10 minutes, and cooled (0° C.). A solution of 1-azabicyclo[3.3.1]nonane-5-methanamine (0.82 g, 5.3 mmol) in tetrahydrofuran (3 mL) was added dropwise, and stirring was continued at room temperature for 18 hours. The suspension was diluted with enough methanol to dissolve the solid, then the solution was filtered through a short column of alumina (eluted with 20% methanol/tetrahydrofuran). The filtrate was concentrated in vacuo, triturated from cold ether, and recrystallized from acetonitrile to afford 1.29 g (73%) of colorless crystals; mp 188°-190° C. (second phase), first phase melting point 175° C.

Fuente