반응 #5475

반응 방정식

1-azabicyclo[3.3.1]nonane-5-methanamine

4-amino-5-chloro-2-(2-methoxyethoxy)benzoic acid

1,1'-carbonyldiimidazole

→

colorless crystals

수율 49.0%

4-Amino-N-(1-azabicyclo[3.3.1]non-5-ylmethyl)-5-chloro-2-(2-methoxyethoxy)benzamide

수율 49.0%

용매

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   기타degassed under a stream of nitrogen over 10 minutes
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITwas continued at room temperature for 18 hours
4. 4
   농축The solution was concentrated in vacuo
5. 5
   세척washed with saturated sodium carbonate (50 mL)
6. 6
   건조The organic solution was dried (Na2SO4)
7. 7
   농축concentrated in vacuo
8. 8
   농축The filtrate was concentrated in vacuo and, at this point
9. 9
   여과filtered
10. 10
    농축the filtrate was concentrated in vacuo
11. 11
    기타triturated from cold ether
12. 12
    기타recrystallized from acetonitrile (2 crops)

실험 절차

A solution of 4-amino-5-chloro-2-(2-methoxyethoxy)benzoic acid (2.09 g, 8.5 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.46 g, 9.0 mmol), stirred for one hour, degassed under a stream of nitrogen over 10 minutes, and cooled (0° C.). A solution of 1-azabicyclo[3.3.1]nonane-5-methanamine (1.36 g, 8.8 mmol) in tetrahydrofuran (5 mL) was added dropwise, and stirring was continued at room temperature for 18 hours. The solution was concentrated in vacuo and the residue was taken up in methylene chloride (100 mL) and washed with saturated sodium carbonate (50 mL). The organic solution was dried (Na2SO4), concentrated in vacuo, and passed through a short column of alumina (eluted with 5% methanol/methylene chloride). The filtrate was concentrated in vacuo and, at this point, appeared to be contaminated with some highly insoluble impurity. The residue was taken up in tetrahydrofuran and filtered, and the filtrate was concentrated in vacuo, triturated from cold ether, and recrystallized from acetonitrile (2 crops) to afford 1.59 g (49%) of colorless crystals; mp 154.0°-155.5° C.

출처