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

HRID 1280989

Reaction equation

HRID 1280989 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-8f36a84adc9b485faf9c12452aabe87d
Source dataset
uspto-grants-2002_09
Patent number
US06451842B1

Linked notes

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