反応 #5473

反応方程式

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

1,1'-carbonyldiimidazole

1-azabicyclo[3.2.1]octane-5-methanamine

→

colorless crystals

収率 70.0%

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

収率 70.0%

溶媒

tetrahydrofuran

反応条件

後処理

1. 1
   その他degassed 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
   濃縮The mixture was concentrated in vacuo
5. 5
   その他partitioned between toluene (100 mL)
6. 6
   workup.ADDITIONcontaining a little 2-propanol and saturated sodium carbonate (50 mL)
7. 7
   その他The organic layer was separated
8. 8
   乾燥the organic solution was dried (Na2SO4)
9. 9
   濃縮concentrated in vacuo
10. 10
    その他triturated from cold ether
11. 11
    その他Recrystallization from acetonitrile (2 crops)

実験手順

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.

出典