反応 #5457

反応方程式

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

lithium diisopropylamide tetrahydorfuran

1-bromo-3-chloropropane

→

product

収率 73.0%

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

収率 73.0%

溶媒

tetrahydrofuran

反応条件

後処理

1. 1
   温度warmed to room temperature over one hour
2. 2
   workup.STIRRINGstirred for 30 minutes
3. 3
   その他Most of the solvent was removed in vacuo
4. 4
   洗浄the organic solution was washed with saturated sodium bicarbonate (150 mL)
5. 5
   抽出The aqueous solution was extracted with ether (2×50 mL)
6. 6
   乾燥the combined organic solution was dried (MgSO4)
7. 7
   濃縮concentrated in vacuo
8. 8
   workup.DISSOLUTIONThe concentrated filtrate was dissolved in anhydrous methylene chloride (25 mL)
9. 9
   温度cooled (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
    濃縮concentrated in vacuo
13. 13
    その他The residue was partitioned between 1.25N sodium carbonate (75 mL) and methylene chloride (100 mL)
14. 14
    その他the organic layer was separated
15. 15
    抽出The aqueous solution was extracted with methylene chloride (2×50 mL)
16. 16
    乾燥the combined organic solution was dried (Na2SO4)
17. 17
    濃縮concentrated in vacuo
18. 18
    workup.ADDITIONtreated with a little charcoal
19. 19
    ろ過filtered
20. 20
    濃縮The filtrate was concentrated in vacuo
21. 21
    workup.DISTILLATIONthe residue was distilled (bp 0.6 83°-85° C.)

実験手順

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.

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