تفاعل #5475

معادلة التفاعل

1-azabicyclo[3.3.1]nonane-5-methanamine

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

1,1'-carbonyldiimidazole

→

colorless crystals

المردود 49.0%

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

المردود 49.0%

المذيبات

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىdegassed 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
   تركيزThe solution was concentrated in vacuo
5. 5
   غسيلwashed with saturated sodium carbonate (50 mL)
6. 6
   تجفيفThe organic solution was dried (Na2SO4)
7. 7
   تركيزconcentrated in vacuo
8. 8
   تركيزThe filtrate was concentrated in vacuo and, at this point
9. 9
   ترشيحfiltered
10. 10
    تركيزthe filtrate was concentrated in vacuo
11. 11
    أخرىtriturated from cold ether
12. 12
    أخرىrecrystallized from acetonitrile (2 crops)

الإجراء التجريبي

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.

المصدر