Reaktion #5478

Reaktionsgleichung

n-butyllithium hexane

1-azabicyclo[3.2.1]octane-5-methanol

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

1,1'-carbonyldiimidazole

→

colorless solid

Ausbeute 47.3%

4-Amino-5-chloro-2-methoxybenzoic acid 1-azabicyclo[3.2.1]oct-5-ylmethyl ester

Ausbeute 47.3%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigedegassed under a stream of nitrogen over 10 minutes
2. 2
   workup.STIRRINGstirred for 30 minutes
3. 3
   Einengenconcentrated in vacuo
4. 4
   SonstigeThe above degassed solution
5. 5
   Sonstigewas transferred into this solution by syringe
6. 6
   workup.STIRRINGthe mixture was stirred at room temperature for 65 hours and at 50° C. for one hour
7. 7
   Einengenconcentrated in vacuo
8. 8
   SonstigeThe residue was partitioned between toluene (100 mL)
9. 9
   workup.ADDITIONcontaining a little 2-propanol and saturated aqueous sodium carbonate (50 mL)
10. 10
    Sonstigethe organic layer was separated
11. 11
    ExtraktionThe aqueous solution was extracted with toluene (2×50 mL)
12. 12
    workup.ADDITIONcontaining a little 2-propanol
13. 13
    Trocknenthe combined organic solution was dried (Na2SO4)
14. 14
    Einengenconcentrated in vacuo
15. 15
    FiltrationThe residue was filtered through alumina (
16. 16
    Wascheneluted with 2% methanol/tetrahydrofuran
17. 17
    Sonstigewith 35% methanol/tetrahydrofuran to collect product), and the filtrate
18. 18
    Einengenwas concentrated in vacuo
19. 19
    Sonstigetriturated from cold ether
20. 20
    SonstigeRecrystallization from ethyl acetate/hexane

Vorschrift

A solution of 4-amino-5-chloro-2-methoxybenzoic acid (1.62 g, 8.0 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.38 g, 8.5 mmol), stirred one hour, and degassed under a stream of nitrogen over 10 minutes. Meanwhile, a cooled (-10° C.) solution of 1-azabicyclo[3.2.1]octane-5-methanol (1.20 g, 8.5 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated (via syringe) with 2.50N n-butyllithium/hexane (8.25 mmol), stirred for 30 minutes, concentrated in vacuo, and taken up in anhydrous tetrahydrofuran (10 mL) under nitrogen. The above degassed solution was transferred into this solution by syringe, and the mixture was stirred at room temperature for 65 hours and at 50° C. for one hour, then concentrated in vacuo. The residue was partitioned between toluene (100 mL) containing a little 2-propanol and saturated aqueous sodium carbonate (50 mL), and the organic layer was separated. The aqueous solution was extracted with toluene (2×50 mL) containing a little 2-propanol, and the combined organic solution was dried (Na2SO4) and concentrated in vacuo. The residue was filtered through alumina (eluted with 2% methanol/tetrahydrofuran, then with 35% methanol/tetrahydrofuran to collect product), and the filtrate was concentrated in vacuo and triturated from cold ether. Recrystallization from ethyl acetate/hexane afforded 1.23 g (47%) of a colorless solid; mp 131°-133° C.

Quelle