Iodoethane → N-[4-(1-diphenylmethyl-piperidin-4-yl)-butyl]-N-ethyl-3-(pyridin-3-yl)-propionamide

HRID 1178407Notes

Reaction equation

HRID 1178407 reaction equation
[H-].[Na+].[C:3]1([CH:9]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:10]2[CH2:15][CH2:14][CH:13]([CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21](=[O:30])[CH2:22][CH2:23][C:24]3[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=3)[CH2:12][CH2:11]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:37](I)[CH3:38]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:31]1([CH:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:10]2[CH2:15][CH2:14][CH:13]([CH2:16][CH2:17][CH2:18][CH2:19][N:20]([CH2:37][CH3:38])[C:21](=[O:30])[CH2:22][CH2:23][C:24]3[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=3)[CH2:12][CH2:11]2)[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

6

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 9846838N-[4-(1-diphenylmethylpiperidin-4-yl)-butyl]-3-(pyridin-3-yl)-propionamide

Product 1

HCID 18431542N-[4-(1-diphenylmethyl-piperidin-4-yl)-butyl]-N-ethyl-3-(pyridin-3-yl)-propionamide

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

0.79 g (26.3 mmol) 80% sodium hydride are suspended in 30 ml DMF and 10.0 g (22.0 mmol) N-[4-(1-diphenylmethyl-piperidin-4-yl)-butyl]-3-(pyridin-3-yl) -propionamide (substance 54) are added. The mixture is warmed to ca. 30° C. and, after addition of 0.2 g tetrabutyl ammonium iodide, this is stirred for one hour. Subsequently, 2.0 ml (24.1 mmol) ethyl iodide is added at RT (foam development) and the orange-brown suspension is stirred at RT overnight. Excess sodium hydride is destroyed by addition of 1 ml water and the mixture is concentrated under vacuum to a large extent. The residue is dispersed between 50 ml water and 100 ml dichloromethane. The organic phase is dried over sodium sulfate and the solvent is removed under vacuum. The residue is chromatographically purified three times over silica gel with CHCl3/CH3OH (97/3 and 100/0 to 97/3 and 98/2) and crystallized from 10 ml 1-chlorobutane/petroleum ether (3/7) after drawing off the solvent. Beige colored crystals with an MP of 72-74° C.; yield 3.6 g (34%).

Workup

  1. stirringthe orange-brown suspension is stirred at RT overnight
  2. customExcess sodium hydride is destroyed by addition of 1 ml water
  3. concentrationthe mixture is concentrated under vacuum to a large extent
  4. additionThe residue is dispersed between 50 ml water and 100 ml dichloromethane
  5. dry with materialThe organic phase is dried over sodium sulfate
  6. customthe solvent is removed under vacuum
  7. customThe residue is chromatographically purified three times over silica gel with CHCl3/CH3OH (97/3 and 100/0 to 97/3 and 98/2)
  8. customcrystallized from 10 ml 1-chlorobutane/petroleum ether (3/7)

Sources & evidence

ORD record
ord-a02579914f4a4dc98d417be761309716
Source dataset
uspto-grants-2007_10
Patent number
US07276524B2

Reaction notes

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