反応 #5475

反応方程式

1-azabicyclo[3.3.1]nonane-5-methanamine

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

1,1'-carbonyldiimidazole

→

colorless crystals

収率 49.0%

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

収率 49.0%

溶媒

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   その他degassed 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
   濃縮The solution was concentrated in vacuo
5. 5
   洗浄washed with saturated sodium carbonate (50 mL)
6. 6
   乾燥The organic solution was dried (Na2SO4)
7. 7
   濃縮concentrated in vacuo
8. 8
   濃縮The filtrate was concentrated in vacuo and, at this point
9. 9
   ろ過filtered
10. 10
    濃縮the filtrate was concentrated in vacuo
11. 11
    その他triturated from cold ether
12. 12
    その他recrystallized from acetonitrile (2 crops)

実験手順

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.

出典