Benzyl Chloride → N-Benzyl-4-Acetyl4-(4-Chlorobenzyl)-piperidine

HRID 53233Notes

Reaction equation

HRID 53233 reaction equation
Cl.[C:2]([C:5]1([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)(=[O:4])[CH3:3].C(=O)(O)[O-].[Na+].[CH2:24](Cl)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C(#N)C>[CH2:24]([N:8]1[CH2:7][CH2:6][C:5]([C:2](=[O:4])[CH3:3])([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=2)[CH2:10][CH2:9]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 7503Benzyl ChlorideHCID 516892Sodium Bicarbonate2×HCID 19962172HCID 19962172, compound

Product 1

HCID 19962174N-Benzyl-4-Acetyl4-(4-Chlorobenzyl)-piperidineYield 98.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of 4-Acetyl-4-(4-chlorobenzyl)-piperidine hydrochloride (0.600 g, 2.09 mmol) in acetonitrile (20 mL) was treated with solid sodium bicarbonate (200 mg, xs) and benzyl chloride (292 mg, 2.3 mol) and heated to reflux for 3 hours. The reaction was then cooled to room temperature, poured into saturated aqueous sodium bicarbonate (200 mL) and extracted with ethyl acetate (3×100 mL). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated at reduced pressure. The residue was chromatographed on silica gel eluting with 2% Methanol/chloroform to give 706 mg of the title compound. 1H NMR CDCl3 δ 7.25 (m, 5H), 7.22 (d, J=8.5 Hz, 2H), 6.96 (d, J=8.5 Hz, 2H), 3.45 (s, 2H), 2.78 (s 2H), 2.76 (m, 2H), 2.20-2.0 (m, 4H), 2.06 (s, 3H), 1.75-1.50 (m, 2H).

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 hours
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated at reduced pressure
  7. customThe residue was chromatographed on silica gel eluting with 2% Methanol/chloroform

Sources & evidence

ORD record
ord-20f2c041e65649e298d403d71c72c176
Source dataset
uspto-grants-1997_04
Patent number
US05618830

Reaction notes

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