반응 #5474

반응 방정식

1-azabicyclo[3.3.1]nonane-5-methanamine

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

1,1'-carbonyldiimidazole

→

colorless crystals

수율 73.3%

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

수율 73.3%

용매

tetrahydrofuran

methanol

tetrahydrofuran

반응 조건

후처리

1. 1
   기타degassed 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
   여과the solution was filtered through a short column of alumina (eluted with 20% methanol/tetrahydrofuran)
6. 6
   농축The filtrate was concentrated in vacuo
7. 7
   기타triturated from cold ether
8. 8
   기타recrystallized from acetonitrile

실험 절차

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.

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