Piperidine → 2-[4-(2-Methyl-3-piperidin-1-ylpropoxy)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-ene

HRID 251466Notes

Reaction equation

HRID 251466 reaction equation
Cl[CH2:2][CH:3]([CH3:22])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[O:16][CH2:15][C:14]3([CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[N:13]=2)=[CH:8][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[NH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1>C(#N)C.[I-].[Na+]>[CH3:22][CH:3]([CH2:2][N:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[O:16][CH2:15][C:14]3([CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[N:13]=2)=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 11430Potassium CarbonateHCID 119509122-[4-(3-Chloro-2-methylpropoxy)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-ene

Product 1

HCID 119500202-[4-(2-Methyl-3-piperidin-1-ylpropoxy)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-eneYield 40%

Reagents, catalysts & solvents 2

HCID 5238Sodium IodideCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of 2-[4-(3-chloro-2-methylpropoxy)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-ene ax64 (0.35 g, 1.1 mmol, 1 eq) in acetonitrile (20 ml) is treated with potassium carbonate (0.3 g, 2.2 mmol, 2 eq), sodium iodide (0.01 g, 0.073 mmol, 0.07 eq) and piperidine (0.52 ml, 5.2 mmol, 4.7 eq), and the mixture is stirred at reflux for 5 days. After this time, the mixture is concentrated, taken up in ethyl acetate and washed with water. The organic layer is dried over magnesium sulfate and concentrated to dryness to give 0.36 g of a yellow oil. This crude product is purified by flash chromatography over silica gel (eluent: dichloromethane/methanol/ammonia 96:3.6:0.4) to give 0.13 g of 2-[4-(2-methyl-3-piperidin-1-ylpropoxy)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-ene 38 as a colorless oil.

Workup

  1. temperatureat reflux for 5 days
  2. concentrationAfter this time, the mixture is concentrated
  3. washwashed with water
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-3d28869dfeec4d2788912f5df584a4e7
Source dataset
uspto-grants-2011_01
Patent number
US07863450B2

Reaction notes

Loading…