Réaction #5473

Équation de réaction

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

1,1'-carbonyldiimidazole

1-azabicyclo[3.2.1]octane-5-methanamine

→

colorless crystals

Rendement 70.0%

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

Rendement 70.0%

Solvants

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Autredegassed 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
   ConcentrationThe mixture was concentrated in vacuo
5. 5
   Autrepartitioned between toluene (100 mL)
6. 6
   workup.ADDITIONcontaining a little 2-propanol and saturated sodium carbonate (50 mL)
7. 7
   AutreThe organic layer was separated
8. 8
   Séchagethe organic solution was dried (Na2SO4)
9. 9
   Concentrationconcentrated in vacuo
10. 10
    Autretriturated from cold ether
11. 11
    AutreRecrystallization from acetonitrile (2 crops)

Mode opératoire

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.

Source