반응 #5457

반응 방정식

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

lithium diisopropylamide tetrahydorfuran

1-bromo-3-chloropropane

→

product

수율 73.0%

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

수율 73.0%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   온도warmed to room temperature over one hour
2. 2
   workup.STIRRINGstirred for 30 minutes
3. 3
   기타Most of the solvent was removed in vacuo
4. 4
   세척the organic solution was washed with saturated sodium bicarbonate (150 mL)
5. 5
   추출The aqueous solution was extracted with ether (2×50 mL)
6. 6
   건조the combined organic solution was dried (MgSO4)
7. 7
   농축concentrated in vacuo
8. 8
   workup.DISSOLUTIONThe concentrated filtrate was dissolved in anhydrous methylene chloride (25 mL)
9. 9
   온도cooled (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
    농축concentrated in vacuo
13. 13
    기타The residue was partitioned between 1.25N sodium carbonate (75 mL) and methylene chloride (100 mL)
14. 14
    기타the organic layer was separated
15. 15
    추출The aqueous solution was extracted with methylene chloride (2×50 mL)
16. 16
    건조the combined organic solution was dried (Na2SO4)
17. 17
    농축concentrated in vacuo
18. 18
    workup.ADDITIONtreated with a little charcoal
19. 19
    여과filtered
20. 20
    농축The filtrate was concentrated in vacuo
21. 21
    workup.DISTILLATIONthe residue was distilled (bp 0.6 83°-85° C.)

실험 절차

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.

출처