تفاعل #5473

معادلة التفاعل

4-amino-5-chloro-2-methoxybenzoic acid

1,1'-carbonyldiimidazole

1-azabicyclo[3.2.1]octane-5-methanamine

→

colorless crystals

المردود 70.0%

4-Amino-N-(1-azabicyclo[3.2.1]oct-5ylmethyl)-5-chloro-2-methoxybenzamide

المردود 70.0%

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىdegassed under a stream of nitrogen for 10 minutes
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITwas continued at room temperature for 18 hours and at 50° C. for one hour
4. 4
   تركيزThe mixture was concentrated in vacuo
5. 5
   أخرىpartitioned between toluene (100 mL)
6. 6
   workup.ADDITIONcontaining a little 2-propanol and saturated sodium carbonate (50 mL)
7. 7
   أخرىThe organic layer was separated
8. 8
   تجفيفthe organic solution was dried (Na2SO4)
9. 9
   تركيزconcentrated in vacuo
10. 10
    أخرىtriturated from cold ether
11. 11
    أخرىRecrystallization from acetonitrile (2 crops)

الإجراء التجريبي

A suspension of 4-amino-5-chloro-2-methoxybenzoic acid (1.72 g, 8.5 mmol) in anhydrous tetrahydrofuan (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.46 g, 9.0 mmol), stirred for one hour, then degassed under a stream of nitrogen for 10 minutes. A solution of 1-azabicyclo[3.2.1]octane-5-methanamine (1.27 g, 9.0 mmol) in anhydrous tetrahydrofuran (8 mL) was added, and stirring was continued at room temperature for 18 hours and at 50° C. for one hour. The mixture was concentrated in vacuo and partitioned between toluene (100 mL) containing a little 2-propanol and saturated sodium carbonate (50 mL). The organic layer was separated and the organic solution was dried (Na2SO4), concentrated in vacuo, and triturated from cold ether. Recrystallization from acetonitrile (2 crops) afforded 1.92 g (70%) of colorless crystals; mp 185°-187° C.

المصدر