Allyl bromide → Ethyl 1-[(phenylmethoxy)carbonyl]-α-2-propen-1-yl-4-piperidineacetate

HRID 1725643Notes

Reaction equation

HRID 1725643 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[CH2:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:8][CH2:7]1)[CH3:2].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH2:33](Br)[CH:34]=[CH2:35]>C1COCC1>[CH2:1]([O:3][C:4]([CH:5]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:13])[CH2:8][CH2:7]1)[CH2:35][CH:34]=[CH2:33])=[O:22])[CH3:2]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 12902702Benzyl 4-(2-ethoxy-2-oxoethyl)piperidine-1-carboxylate

Product 1

HCID 67441606Ethyl 1-[(phenylmethoxy)carbonyl]-α-2-propen-1-yl-4-piperidineacetateYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a −78 □C solution of benzyl 4-(2-ethoxy-2-oxoethyl)piperidine-1-carboxylate (5.02 g, 16.4 mmol) in THF (90 mL) was added lithium hexamethyldisilazide (1.0 M in THF, 18.1 mL, 18.1 mmol). After 1 h allyl bromide (2.19 g, 18.1 mmol) was added, the reaction stirred at this temperature for 0.5 h, then warmed to 25 □C. After 3 h the reaction was quenched by the addition of saturated aqueous ammonium chloride and extracted with ethyl acetate (2×). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of 0 to 60% EtOAc:hexanes to give the title compound (4.08 g). MS: m/z=346.1 (M+1).

Workup

  1. temperaturewarmed to 25 □C
  2. customAfter 3 h the reaction was quenched by the addition of saturated aqueous ammonium chloride
  3. extractionextracted with ethyl acetate (2×)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with a gradient of 0 to 60% EtOAc

Sources & evidence

ORD record
ord-ec2554ec4f1e41949c846a9d55c50a10
Source dataset
uspto-grants-2009_02
Patent number
US07491713B2

Reaction notes

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