Ethyl 4-piperidinecarboxylate → ethyl N-(2,6-dimethoxyphenylmethyl)piperidin-4-ylcarboxylate

HRID 866058Notes

Reaction equation

HRID 866058 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH2:11]Br.[NH:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]1.[F-].[K+]>C(#N)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH2:11][N:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 70770Ethyl 4-piperidinecarboxylateHCID 522689Potassium FluorideHCID 155569582-(Bromomethyl)-1,3-dimethoxybenzene

Product 1

HCID 19040928ethyl N-(2,6-dimethoxyphenylmethyl)piperidin-4-ylcarboxylateYield 16.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A stirred solution of 4.7 grams (0.020 mole) of 2,6-dimethoxyphenylmethyl bromide, 3.2 grams (0.020 mole) of ethyl piperidin-4-ylcarboxylate, and 23.5 grams (0.200 mole) of 50% potassium fluoride on Celite® filter aid in 100 mL of acetonitrile was heated at reflux for about 18 hours, after which the reaction mixture was cooled and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with mixtures of ethyl acetate in hexane as eluants. The product-containing fractions were combined and concentrated under reduced pressure to a residue. The residue was analyzed using thin layer chromatography, which indicated that the residue was impure. The residue was again subjected to column chromatography on silica gel, with mixtures of ethyl acetate in hexane and methanol in ethyl acetate as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding about one gram of ethyl N-(2,6-dimethoxyphenylmethyl)piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for about 18 hours
  3. temperatureafter which the reaction mixture was cooled
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure to a residue, which
  6. concentrationconcentrated under reduced pressure to a residue
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9392da3f598a4280866734ccf0ec5d14
Source dataset
uspto-grants-1996_10
Patent number
US05569664

Reaction notes

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