Ethyl Bromide → 4-(4-Ethylphenyl)-1-methyl-piperidine

HRID 1448980Notes

Reaction equation

HRID 1448980 reaction equation
[Mg].Cl[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[CH2:16](Br)[CH3:17].[OH-].[Na+]>CI.CCOCC.[Cu]I>[CH2:16]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)[CH3:17]

Participants

8

Reactant 4

HCID 6332Ethyl BromideHCID 14798Sodium HydroxideHCID 5462224Magnesium2×HCID 128501074-(4-Chlorophenyl)-1-methylpiperidine

Product 1

HCID 128501084-(4-Ethylphenyl)-1-methyl-piperidine

Reagents, catalysts & solvents 3

HCID 6328Methyl iodideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolvent2×

Procedure

A few drops of methyl iodide are added, under nitrogen, to a suspension of 0.5 g of magnesium chips covered with a small amount of absolute ether and, after the reaction has subsided, there is added dropwise at 30° to 35° a solution of 4.2 g of 4-(4-chlorophenyl)-1-methyl-piperidine in 20 ml of absolute ether. When the major part of the magnesium has been dissolved, 100 mg of copper(I)iodide is added; the temperature is lowered to -10°, 2.5 g of ethyl bromide is added, and stirring is maintained over night at -10° to 0°. An addition of 50 ml of 2 N sodium hydroxide solution is then made, the mixture is saturated with sodium chloride, and extraction is performed three times with 50 ml of ether each time. The organic phases are combined, washed until neutral, dried over sodium sulphate and concentrated in vacuo. Distillation of the residue under high vacuum, and chromatography of the fraction boiling at 90°-100° (0.03 mm) on silica gel with chloroform and a small amount of methanol as the eluant yield crude 4-(4-ethylphenyl)-1-methyl-piperidine, which is converted into the hydrochloride, m.p. 209°-210°.

Workup

  1. customis lowered to -10°
  2. temperatureis maintained over night at -10° to 0°
  3. extractionthe mixture is saturated with sodium chloride, and extraction
  4. washwashed until neutral,
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in vacuo
  7. distillationDistillation of the residue under high vacuum, and chromatography of the fraction boiling at 90°-100° (0.03 mm) on silica gel with chloroform

Sources & evidence

ORD record
ord-bae8e71a22294f8ab0e35e63155a88d5
Source dataset
uspto-grants-1980_02
Patent number
US04188396

Reaction notes

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