Dimethylformamide → Ethyl 1-(4-methoxybenzyl)piperidine-3-carboxylate

HRID 228492Notes

Reaction equation

HRID 228492 reaction equation
[NH:1]1[CH2:11][CH2:10][CH2:9][CH:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:2]1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C.[CH3:23][O:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Cl)=[CH:27][CH:26]=1>C(OCC)(=O)C>[CH2:7]([O:6][C:4]([CH:3]1[CH2:9][CH2:10][CH2:11][N:1]([CH2:29][C:28]2[CH:31]=[CH:32][C:25]([O:24][CH3:23])=[CH:26][CH:27]=2)[CH2:2]1)=[O:5])[CH3:8]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 98969Ethyl nipecotate

Product 1

HCID 3160450Ethyl 1-(4-methoxybenzyl)piperidine-3-carboxylateYield 82.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Combine Ethyl nipecotate (9.9 mL, 63.6 mmol), K2CO3 (13.2 g, 95.4 mmol), and DMF (300 mL) at room temperature under a Nitrogen atmosphere. Heat reaction mixture to 70° C. for 30 minutes then add 4-Methoxybenzyl chloride (9.5 mL, 69.9 mmol). Stir the reaction for 5 hours at 70° C. then cool the reaction mixture to room temperature and stir for an additional 12 hours. Add Ethyl acetate to the reaction mixture and extract with water and then brine. Dry the organic layer over Na2SO4. Concentrate under reduced pressure and flash chromatograph using 3:1 Hexanes:Ethyl acetate to give 14.6 g (82% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 1.2 (3H, t), 1.4-1.6 (2H, m), 1.6-1.7 (1H, m), 1.9-2.1 (2H, m), 2.2 (1H, t), 1.5-1.8 (2H, m), 2.9 (1H, d), 3.5 (2H, q), 3.8 (3H, s), 4.1 (2H, dd), 6.8 (2H, d), 7.2 (2H, d); MS m/z 278 (M+1).

Workup

  1. customat room temperature
  2. temperatureHeat
  3. customreaction mixture to 70° C. for 30 minutes
  4. customthe reaction for 5 hours at 70° C.
  5. stirringstir for an additional 12 hours
  6. extractionAdd Ethyl acetate to the reaction mixture and extract with water
  7. dry with materialDry the organic layer over Na2SO4
  8. concentrationConcentrate under reduced pressure and flash chromatograph

Sources & evidence

ORD record
ord-53741a6a6ced4653ace718304312e7dc
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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