1-benzyl-N-methoxy-N-methylpiperidine-4-carboxamide → 1-(1-Benzylpiperidin-4-yl)pent-4-en-1-one

HRID 579582Notes

Reaction equation

HRID 579582 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](N(OC)C)=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:20]([Mg]Br)[CH2:21][CH:22]=[CH2:23]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:15])[CH2:23][CH2:22][CH:21]=[CH2:20])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 211930301-benzyl-N-methoxy-N-methylpiperidine-4-carboxamideHCID 178418797HCID 178418797, compound

Product 1

HCID 668336681-(1-Benzylpiperidin-4-yl)pent-4-en-1-oneYield 58.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-benzyl-N-methoxy-N-methylpiperidine-4-carboxamide (8.88 g, 33.0 mmol) in THF (40 mL, 0.8 M) was cooled to 0° C. and treated with a 0.5 M solution of 3-butenylmagnesium bromide (51 mmol, 102 mL) in a dropwise manner. After stirring for 4 h the reaction was quenched with 1 N HCl (24 mL), neutralized with 5% aqueous sodium bicarbonate and diluted with ethyl acetate. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride, dried over MgSO4, and concentrated in vacuo. The residue was chromatographed on silica (2-20% methanol in dichloromethane) to afford the desired product (4.95 g, 57%). Rf 0.22 (10% MeOH/CH2Cl2). 1H NMR (CDCl3, 300 MHz) δ 7.38-7.21 (m, 5H), 5.82-5.76 (m, 1H), 5.15-4.95 (m, 2H), 3.50 (s, 2H), 2.91 (d, J=11.2 Hz, 2H), 2.54 (t, J=7.3 Hz, 2H), 2.39-2.23 (m, 3H), 2.06-1.97 (m, 2H), 1.82-1.61 (m, 4H). ESI MS found for C17H23NO m/z [258.2 (M+1)].

Workup

  1. customwas quenched with 1 N HCl (24 mL)
  2. additiondiluted with ethyl acetate
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with ethyl acetate
  5. washThe combined organic layers were washed with saturated aqueous sodium chloride
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was chromatographed on silica (2-20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0c0b0c1fc1ce4706b996c3181b63f857
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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