Benzyl Bromide → Ethyl-1-benzoyl-4-(phenylmethyl)-4-piperidinecarboxylate

HRID 1591150Notes

Reaction equation

HRID 1591150 reaction equation
[C:1]([N:9]1[CH2:14][CH2:13][CH:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:30](Br)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>O1CCCC1>[CH2:18]([O:17][C:15]([C:12]1([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:13][CH2:14][N:9]([C:1](=[O:8])[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:10][CH2:11]1)=[O:16])[CH3:19]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 735824Ethyl 1-benzoylpiperidine-4-carboxylateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 10545888Ethyl-1-benzoyl-4-(phenylmethyl)-4-piperidinecarboxylateYield 118.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 7.84 g (30.0 mmoles) ethyl 1-benzoyl-4-piperidinecarboxylate (G. R. Clemo and E. Hoggarth, J. Chem. Soc., 41, (1941) in 60 ml dry tetrahydrofuran at -78° C. under argon was added dropwise over 10 minutes 33.0 ml (33.0 mmoles) lithium bis(trimethylsilyl)amide in tetrahydrofuran and the resulting solution was stirred 30 minutes. To this solution was added dropwise over 2 minutes 5.64 g (33.0 mmoles) benzyl bromide in 10 ml dry tetrahydrofuran and the resulting solution was stirred overnight while warming from -78° C. to room temperature. The reaction was quenched with 20 ml saturated ammonium chloride solution and extracted with 2×100 ml ethyl acetate. The combined extracts were washed with 20 ml water and brine, dried, and the solvent removed in vacuo to give an oil. The oil was stirred under 25 ml hexane at -15° C., the hexane was decanted and the oil was dried in vacuo to give 12.5 g crude product as a viscous oil;

Workup

  1. stirringthe resulting solution was stirred overnight
  2. temperaturewhile warming from -78° C. to room temperature
  3. customThe reaction was quenched with 20 ml saturated ammonium chloride solution
  4. extractionextracted with 2×100 ml ethyl acetate
  5. washThe combined extracts were washed with 20 ml water and brine
  6. customdried
  7. customthe solvent removed in vacuo
  8. customto give an oil
  9. stirringThe oil was stirred under 25 ml hexane at -15° C.
  10. customthe hexane was decanted
  11. customthe oil was dried in vacuo

Sources & evidence

ORD record
ord-c76a43760d3c466fb61c1fa61da3978e
Source dataset
uspto-grants-1993_04
Patent number
US05206240

Reaction notes

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