Chloroacetyl chloride → N-(1-Benzyl-piperidin-4-yl)-2-chloro-N-isopropyl-acetamide

HRID 659079Notes

Reaction equation

HRID 659079 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH:15]([CH3:17])[CH3:16])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:27][CH2:28][C:29](Cl)=[O:30]>ClCCl>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH:15]([CH3:17])[CH3:16])[C:29](=[O:30])[CH2:28][Cl:27])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 107283101-Benzyl-N-isopropylpiperidin-4-amine

Product 1

HCID 66565165N-(1-Benzyl-piperidin-4-yl)-2-chloro-N-isopropyl-acetamideYield 50.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a mixture of 1-benzyl-4-(isopropylamino)piperidine (8 g, 34.45 mmol) and DIPEA (7.2 mL, 41.3 mmol) in 200 mL of dichloromethane was added dropwise a solution of 2-chloroacetyl chloride (3.01 mL, 37.9 mmol) in dichloromethane (400 mL) at 0° C. The reaction mixture was stirred at 0° C. for 15 min and then at room temperature for 2 h. The reaction mixture was then washed with saturated sodium bicarbonate, brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by flash column chromatography (ethyl acetate/hexane/triethylamine: 42.5/56.5/1) to give 5.35 g of the title intermediate as a viscous oil (50% yield).

Workup

  1. waitat room temperature for 2 h
  2. washThe reaction mixture was then washed with saturated sodium bicarbonate, brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by flash column chromatography (ethyl acetate/hexane/triethylamine: 42.5/56.5/1)

Sources & evidence

ORD record
ord-64ceaa9e27b34369b9ec8a7b788eef19
Source dataset
uspto-grants-2011_12
Patent number
US08080565B2

Reaction notes

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