1,4-Butanediol → N-(1-Benzylpiperdin-4-yl)-N-isopropyl 2-(4-Hydroxybut-1-oxy)acetamide

HRID 1181519Notes

Reaction equation

HRID 1181519 reaction equation
[CH2:1]([OH:6])[CH2:2][CH2:3][CH2:4][OH:5].[OH-].[Na+].[CH2:9]([N:16]1[CH2:21][CH2:20][CH:19]([N:22]([CH:27]([CH3:29])[CH3:28])[C:23](=[O:26])[CH2:24]Cl)[CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(O)(C)(C)C>[CH2:9]([N:16]1[CH2:17][CH2:18][CH:19]([N:22]([CH:27]([CH3:29])[CH3:28])[C:23](=[O:26])[CH2:24][O:5][CH2:4][CH2:3][CH2:2][CH2:1][OH:6])[CH2:20][CH2:21]1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 80641,4-ButanediolHCID 14798Sodium Hydroxide2×HCID 66565165N-(1-Benzyl-piperidin-4-yl)-2-chloro-N-isopropyl-acetamide

Product 1

HCID 67428348N-(1-Benzylpiperdin-4-yl)-N-isopropyl 2-(4-Hydroxybut-1-oxy)acetamideYield 81%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent2×

Procedure

1,4-Butanediol (16 mL, 178 mmol) was refluxed with sodium hydroxide (970 mg, 24.3 mmol) in tert-butanol (8 mL) for 2 h at which time the solid sodium hydroxide had dissolved. The solution was then cooled to room temperature and a solution of N-(1-benzylpiperdin-4-yl)-N-isopropyl 2-chloroacetamide (5.0 g, 16.2 mmol) in tert-butanol (8 mL) was added dropwise. The reaction mixture was then stirred at room temperature overnight. After removal of tert-butanol under reduced pressure, the residue was dissolved in dichloromethane and this solution washed with sodium bicarbonate, water and brine. The organic layer was then dried over magnesium sulfate and concentrated. The residue was purified by flash column chromatography (dichloromethane/methanol/ammonium hydroxide: 90/9/1) to give 4.73 g of the title intermediate as a viscous oil (81% yield).

Workup

  1. dissolutionhad dissolved
  2. customAfter removal of tert-butanol under reduced pressure
  3. dissolutionthe residue was dissolved in dichloromethane
  4. washthis solution washed with sodium bicarbonate, water and brine
  5. dry with materialThe organic layer was then dried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (dichloromethane/methanol/ammonium hydroxide: 90/9/1)

Sources & evidence

ORD record
ord-893795456c6748fa88917214a6d5fe7a
Source dataset
uspto-grants-2007_10
Patent number
US07285564B2

Reaction notes

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