Reaktion #5473

Reaktionsgleichung

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

1,1'-carbonyldiimidazole

1-azabicyclo[3.2.1]octane-5-methanamine

→

colorless crystals

Ausbeute 70.0%

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

Ausbeute 70.0%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigedegassed 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
   EinengenThe mixture was concentrated in vacuo
5. 5
   Sonstigepartitioned between toluene (100 mL)
6. 6
   workup.ADDITIONcontaining a little 2-propanol and saturated sodium carbonate (50 mL)
7. 7
   SonstigeThe organic layer was separated
8. 8
   Trocknenthe organic solution was dried (Na2SO4)
9. 9
   Einengenconcentrated in vacuo
10. 10
    Sonstigetriturated from cold ether
11. 11
    SonstigeRecrystallization from acetonitrile (2 crops)

Vorschrift

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.

Quelle