1-Bromo-4-chlorobutane → Ethyl 6-chloro-2-ethoxycarbonyl-2-(p-toluoylamino)hexanoate

HRID 857233Notes

Reaction equation

HRID 857233 reaction equation
[Na].[C:2]1([CH3:22])[CH:7]=[CH:6][C:5]([C:8]([NH:10][CH:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:9])=[CH:4][CH:3]=1.Br[CH2:24][CH2:25][CH2:26][CH2:27][Cl:28]>C(O)C>[Cl:28][CH2:27][CH2:26][CH2:25][CH2:24][C:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])([NH:10][C:8]([C:5]1[CH:6]=[CH:7][C:2]([CH3:22])=[CH:3][CH:4]=1)=[O:9])[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

5

Reactant 3

HCID 813641-Bromo-4-chlorobutaneHCID 5360545SodiumHCID 17447783Diethyl p-toluoylaminomalonate

Product 1

HCID 21866781Ethyl 6-chloro-2-ethoxycarbonyl-2-(p-toluoylamino)hexanoateYield 54.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium (6.42 g) was dissolved in 390 ml of ethanol at room temperature. To the solution was added 78.0 g of diethyl p-toluoylaminomalonate, and 47.9 g of 1-bromo-4-chlorobutane was added dropwise under heating to reflux. The mixture was heated to reflux for 20 hours. The reaction solution was concentrated. To the residue was added water, and the mixture was washed with ethyl acetate. After washing with 10% hydrochloric acid and water sequentially, the solution was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (Wakogel® C-200, n-hexane: ethyl acetate=9:1) to provide 55.7 g of the objective compound as colorless oil.

Workup

  1. additionwas added dropwise
  2. temperatureunder heating to reflux
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 20 hours
  5. concentrationThe reaction solution was concentrated
  6. additionTo the residue was added water
  7. washthe mixture was washed with ethyl acetate
  8. washAfter washing with 10% hydrochloric acid and water sequentially
  9. dry with materialthe solution was dried over anhydrous magnesium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel column chromatography (Wakogel® C-200, n-hexane: ethyl acetate=9:1)

Sources & evidence

ORD record
ord-d6e607109e0a497a9a79d0630c045c72
Source dataset
uspto-grants-2006_12
Patent number
US07144906B2

Reaction notes

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