Water → (4-(Chloromethyl)piperidin-1-yl)(phenyl)methanone

HRID 1005443Notes

Reaction equation

HRID 1005443 reaction equation
[C:1]([N:9]1[CH2:14][CH2:13][CH:12]([CH2:15]O)[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.P(Cl)(Cl)([Cl:25])=O.O>C(Cl)(Cl)Cl>[C:1]([N:9]1[CH2:14][CH2:13][CH:12]([CH2:15][Cl:25])[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 24813Phosphorus oxychlorideHCID 102628704-Piperidinemethanol, 1-benzoyl-

Product 1

HCID 11118098(4-(Chloromethyl)piperidin-1-yl)(phenyl)methanoneYield 53.4%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

In 10 ml of chloroform was dissolved 2.19 g (10 mmol) of N-benzoyl-4-hydroxymethylpiperidine (C) and to the resulting solution were added 0.81 ml (10 mmol) of pyridine and 1.4 ml (15 mmol) of phosphorus oxychloride. The resulting mixture was stirred at room temperature for 24 hours. After the completion of the reaction, thereto was added 10 ml of chloroform and the resulting mixture was poured into 20 ml of iced water to separate an organic layer. The organic layer was washed with 20 ml of water and dried over 3 g of anhydrous magnesium sulfate. Then, the solvent was removed by distillation to obtain 3.18 g of an oily matter. The oily matter was subjected to silica gel column chromatography (stationary phase: 40 g of Silicagel 60 available from Merck KGaA). The fraction eluted with a hexane/ethyl acetate mixture (1:1 (v/v)) was collected. The solvent was removed by distillation from the obtained fraction to obtain 1.27 g of N-benzoyl-4-chloromethylpiperidine (D) as a colorless crystal. The NMR spectrum of this compound coincided with that of the product in Example 3.

Workup

  1. customAfter the completion of the reaction
  2. customto separate an organic layer
  3. washThe organic layer was washed with 20 ml of water
  4. dry with materialdried over 3 g of anhydrous magnesium sulfate
  5. customThen, the solvent was removed by distillation
  6. customto obtain 3.18 g of an oily matter
  7. washThe fraction eluted with a hexane/ethyl acetate mixture (1:1 (v/v))
  8. customwas collected
  9. customThe solvent was removed by distillation from the obtained fraction

Sources & evidence

ORD record
ord-a0bdab79f11f4f7b958ce71ce575ea70
Source dataset
uspto-grants-2000_04
Patent number
US06054586

Reaction notes

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