Reaktion #5457

Reaktionsgleichung

1,3-piperidinedicarboxylic acid 1-(1,1-dimethylethyl) 3-ethyl ester

lithium diisopropylamide tetrahydorfuran

1-bromo-3-chloropropane

→

product

Ausbeute 73.0%

1-Azabicyclo[3.3.1]nonane-5-carboxylic acid ethyl ester

Ausbeute 73.0%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwarmed to room temperature over one hour
2. 2
   workup.STIRRINGstirred for 30 minutes
3. 3
   SonstigeMost of the solvent was removed in vacuo
4. 4
   Waschenthe organic solution was washed with saturated sodium bicarbonate (150 mL)
5. 5
   ExtraktionThe aqueous solution was extracted with ether (2×50 mL)
6. 6
   Trocknenthe combined organic solution was dried (MgSO4)
7. 7
   Einengenconcentrated in vacuo
8. 8
   workup.DISSOLUTIONThe concentrated filtrate was dissolved in anhydrous methylene chloride (25 mL)
9. 9
   Temperaturcooled (10° C.)
10. 10
    workup.ADDITIONtreated dropwise with trifluoroacetic acid (15 mL)
11. 11
    workup.STIRRINGThe solution was stirred for one hour at room temperature, 15 minutes at 45° C.
12. 12
    Einengenconcentrated in vacuo
13. 13
    SonstigeThe residue was partitioned between 1.25N sodium carbonate (75 mL) and methylene chloride (100 mL)
14. 14
    Sonstigethe organic layer was separated
15. 15
    ExtraktionThe aqueous solution was extracted with methylene chloride (2×50 mL)
16. 16
    Trocknenthe combined organic solution was dried (Na2SO4)
17. 17
    Einengenconcentrated in vacuo
18. 18
    workup.ADDITIONtreated with a little charcoal
19. 19
    Filtrationfiltered
20. 20
    EinengenThe filtrate was concentrated in vacuo
21. 21
    workup.DISTILLATIONthe residue was distilled (bp 0.6 83°-85° C.)

Vorschrift

A cooled (-50° C.) solution of 1,3-piperidinedicarboxylic acid 1-(1,1-dimethylethyl) 3-ethyl ester (12.9 g, 50 mmol) in anhydrous tetrahydrofuran (60 mL) was treated (via syringe) with 1.15N lithium diisopropylamide/tetrahydorfuran (52 mmol), stirred for one hour at -15°±5° C., cooled (-35° C.), treated with 1-bromo-3-chloropropane (10.2 g, 65 mmol), warmed to room temperature over one hour, and stirred for 30 minutes. Most of the solvent was removed in vacuo, replaced with ether, and the organic solution was washed with saturated sodium bicarbonate (150 mL). The aqueous solution was extracted with ether (2×50 mL), and the combined organic solution was dried (MgSO4), concentrated in vacuo, and passed through a short column of alumina (eluted with methylene chloride). The concentrated filtrate was dissolved in anhydrous methylene chloride (25 mL), cooled (10° C.), and treated dropwise with trifluoroacetic acid (15 mL). The solution was stirred for one hour at room temperature, 15 minutes at 45° C., and concentrated in vacuo. The residue was partitioned between 1.25N sodium carbonate (75 mL) and methylene chloride (100 mL), and the organic layer was separated. The aqueous solution was extracted with methylene chloride (2×50 mL), and the combined organic solution was dried (Na2SO4), concentrated in vacuo, taken up in warm hexane, treated with a little charcoal, and filtered. The filtrate was concentrated in vacuo and the residue was distilled (bp 0.6 83°-85° C.) to give 7.2 g (73%) of the product.

Quelle