反応 #5474

反応方程式

1-azabicyclo[3.3.1]nonane-5-methanamine

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

1,1'-carbonyldiimidazole

→

colorless crystals

収率 73.3%

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

収率 73.3%

溶媒

tetrahydrofuran

methanol

tetrahydrofuran

反応条件

後処理

1. 1
   その他degassed 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
   ろ過the solution was filtered through a short column of alumina (eluted with 20% methanol/tetrahydrofuran)
6. 6
   濃縮The filtrate was concentrated in vacuo
7. 7
   その他triturated from cold ether
8. 8
   その他recrystallized from acetonitrile

実験手順

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.

出典