Potassium Carbonate → ethyl N-[2-(4-methoxyphenyl)ethyl]piperidin-4-ylcarboxylate

HRID 866052Notes

Reaction equation

HRID 866052 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]1.Cl[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][CH2:13][N:1]2[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]2)=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 70770Ethyl 4-piperidinecarboxylateHCID 875134-(2-Chloroethyl)phenyl methyl ether

Product 1

HCID 15390165ethyl N-[2-(4-methoxyphenyl)ethyl]piperidin-4-ylcarboxylateYield 25.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

The reaction conditions for N-alkylation taught by G. D. Maynard et al., Bioorganic & Medicinal Chemistry Letters, 3(4), pp. 753-756, 1993, were used in the following preparation. A stirred mixture of 5.0 grams (0.032 mole) of ethyl piperidin-4-ylcarboxylate, 5.4 grams (0.032 mole) of 1-(2-chloroethyl)-4-methoxybenzene and 4.4 grams (0.032 mole) of potassium carbonate in 50 mL of dried N,N-dimethylformamide was heated at 70° C. for about 16 hours. After this time the reaction mixture was cooled and partitioned between diethyl ether and water. The organic layer was separated and washed with water and then with an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with diethyl ether/hexane mixtures as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 2.4 grams of ethyl N-[2-(4-methoxyphenyl)ethyl]piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure.

Workup

  1. customThe reaction conditions for N-alkylation
  2. custom753-756, 1993, were used in the following preparation
  3. temperatureAfter this time the reaction mixture was cooled
  4. custompartitioned between diethyl ether and water
  5. customThe organic layer was separated
  6. washwashed with water
  7. dry with materialThe organic layer was dried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure to a residue, which
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-77ece43cda514b1099cb1a370e432882
Source dataset
uspto-grants-1996_10
Patent number
US05569664

Reaction notes

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