Water → 1-Acetyl-4-{[(4-chlorophenyl)methyl]oxy}piperidine

HRID 1727209Notes

Reaction equation

HRID 1727209 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[H-].[Na+].[Cl:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Cl)=[CH:16][CH:15]=1.O>CN(C)C=O>[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][CH2:18][C:17]2[CH:20]=[CH:21][C:14]([Cl:13])=[CH:15][CH:16]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 77231-Chloro-4-(chloromethyl)benzeneHCID 24758Sodium hydrideHCID 107492911-(4-Hydroxypiperidin-1-yl)ethan-1-one

Product 1

HCID 690562981-Acetyl-4-{[(4-chlorophenyl)methyl]oxy}piperidineYield 84.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

1-Acetylpiperidin-4-ol (Preparation 193, 10 g, 70 mmol) in N,N-dimethylformamide (50 ml) was added dropwise to a stirred suspension of sodium hydride (50% wt dispersion in oil, 4.8 g, 0.1 mol) in N,N-dimethylformamide (50 ml) at room temperature under nitrogen. After stirring the reaction mixture for 3 hours, 4-chlorobenzyl chloride (12.8 g, 80 mmol) in N,N-dimethylformamide (50 ml) was added dropwise and the reaction mixture was stirred for a further 4 h. The solution was filtered and the filtrate was evaporated to give an orange oil. Water was added and the mixture was extracted with petroleum ether (3×50 ml) and then with diethyl ether (3×50 ml). The combined organic extracts were dried (Na2SO4) and concentrated to give the title compound as an orange oil (15.8 g, 84%).

Workup

  1. stirringthe reaction mixture was stirred for a further 4 h
  2. filtrationThe solution was filtered
  3. customthe filtrate was evaporated
  4. customto give an orange oil
  5. extractionthe mixture was extracted with petroleum ether (3×50 ml)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e6a512af005746f9970888d411622068
Source dataset
uspto-grants-2009_02
Patent number
US07494992B2

Reaction notes

Loading…