1-Chloro-4-(chloromethyl)benzene → 3-Carbamoyl-1-(4-chlorobenzyl)piperidine

HRID 279291

Reaction equation

HRID 279291 reaction equation
[NH:1]1[CH2:9][CH2:8][CH2:7][CH:3]([C:4]([NH2:6])=[O:5])[CH2:2]1.CCN(CC)CC.[Cl:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1.C([O-])(O)=O.[Na+]>CC#N.C(O)C.O>[C:4]([CH:3]1[CH2:7][CH2:8][CH2:9][N:1]([CH2:22][C:21]2[CH:24]=[CH:25][C:18]([Cl:17])=[CH:19][CH:20]=2)[CH2:2]1)(=[O:5])[NH2:6]

Participants

8

Reactant 4

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 8471TriethylamineHCID 929803-PiperidinecarboxamideHCID 516892Sodium Bicarbonate

Product 1

HCID 28457973-Carbamoyl-1-(4-chlorobenzyl)piperidineYield 55.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

A solution of nipecotamide (6.40 g, 50 mmol) in CH3CN (150 mL) and ethanol (20 mL) was treated with Et3N (7.0 mL, 50 mmol) and 4-chlorobenzyl chloride (8.05 g, 50 mmol). The reaction mixture was stirred at 50° C. for 16 h. After cooling to room temperature, saturated aqueous NaHCO3 (50 mL) and water (150 mL) was added to the reaction mixture. The mixture was extracted with ethyl acetate (150 mL×3) and the combined organic layers were washed with brine, dried (Na2SO4) and concentrated to give a pale red solid. The crude solid was washed with ether (100 mL) to afford 3-carbamoyl-1-(4-chlorobenzyl)piperidine (6.98 g, 54%).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (150 mL×3)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customto give a pale red solid
  7. washThe crude solid was washed with ether (100 mL)

Sources & evidence

ORD record
ord-6c730d6f69b54ab6a3841806aca31ca0
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Linked notes

Loading…