Benzyl Bromide → Ethyl 1-benzylpiperidine-4-carboxylate

HRID 2408830Notes

Reaction equation

HRID 2408830 reaction equation
[NH:1]1[CH2:11][CH2:10][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[NH4+].[Cl-]>CN(C)C=O>[CH2:8]([O:7][C:5]([CH:4]1[CH2:3][CH2:2][N:1]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:11][CH2:10]1)=[O:6])[CH3:9]

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 70770Ethyl 4-piperidinecarboxylate

Product 1

HCID 90423Ethyl 1-benzylpiperidine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Ethyl isonipecotate (40.0 mL, 0.26 mol), K2CO3, (55 g, 0.4 mol) and N,N-dimethylformamide (200 mL) were combined under nitrogen. The resulting mixture was cooled in an ice bath and benzyl bromide (31.0 mL, 0.26 mol) was added. The reaction mixture was allowed to stir overnight with warming to ambient temperature. A saturated aqueous solution of NH4Cl (500 mL) was added, and the product was extracted twice with ethyl acetate (1 L and 0.5 L). The combined organic layers were washed with saturated aqueous NH4Cl (500 mL) and brine (500 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The resulting crude product was purified by flash chromatography on silica gel (400 g) eluting with hexane/ethyl acetate (1:0 to 4:1) to obtain 1-benzyl-piperidine-4-carboxylic acid ethyl ester. 1H NMR (400 MHz, CDCl3) δ ppm 1.24 (t, J=7.07 Hz, 3 H) 1.69-1.82 (m, 2 H) 1.82-1.92 (m, 2 H) 1.96-2.10 (m, 2 H) 2.20-2.34 (m, 1 H) 2.79-2.91 (m, 2 H) 3.48 (s, 2 H) 4.12 (q, J=7.14 Hz, 2 H) 7.20-7.32 (m, 5 H).

Workup

  1. temperatureThe resulting mixture was cooled in an ice bath
  2. extractionthe product was extracted twice with ethyl acetate (1 L and 0.5 L)
  3. washThe combined organic layers were washed with saturated aqueous NH4Cl (500 mL) and brine (500 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude product was purified by flash chromatography on silica gel (400 g)
  8. washeluting with hexane/ethyl acetate (1:0 to 4:1)

Sources & evidence

ORD record
ord-1cf5b991b558486f8397cd4396ac5a15
Source dataset
uspto-grants-2014_08
Patent number
US08815869B2

Reaction notes

Loading…