2-Chloroethanol → Phenylmethyl 4-(2-chloroethoxy)-3-oxobutanoate

HRID 1727907Notes

Reaction equation

HRID 1727907 reaction equation
[H-].[Na+].[Cl:3][CH2:4][CH2:5][OH:6].[CH2:7]([O:14][C:15](=[O:21])[CH2:16][C:17]([CH2:19]Br)=[O:18])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Cl>C1COCC1>[CH2:7]([O:14][C:15](=[O:21])[CH2:16][C:17]([CH2:19][O:6][CH2:5][CH2:4][Cl:3])=[O:18])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 342-ChloroethanolHCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 12985404HCID 12985404, compound

Product 1

HCID 22570154Phenylmethyl 4-(2-chloroethoxy)-3-oxobutanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4.00 g (21.0 mmol) of acetoacetic acid benzyl ester was dissolved in 40 ml of ether. 1.1 ml (21.0 mmol) of bromine was dropped at 0° C. After stirring at 0° C. for 30 minutes and then at room temperature for 5 hours, about 4 g of ice and sodium carbonate were added so that pH showed 7 or more. The organic layer extracted with ether was washed with water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, concentrated and dried in vacuo to obtain 4-bromoacetoacetic acid benzyl ester. 1.68 g (24.0 mmol) of sodium hydride (60% oily substance) was suspended in 20 ml of THF and 11.7 g (21.0 mmol) of 2-chloroethanol was added at −40° C. 4-bromoacetoacetic acid benzyl ester was dropped at −40° C., gradually heated and stirred at room temperature for 16 hours. After adding 1 N hydrochloric acid and extracting with ethyl acetate, the obtained mixture was washed with water and saturated aqueous sodium chloride solution. The mixture was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by the silica gel chromatography (hexane/ethyl acetate=7/3) to obtain the title compound.

Workup

  1. temperaturegradually heated
  2. extractionextracting with ethyl acetate
  3. washthe obtained mixture was washed with water and saturated aqueous sodium chloride solution
  4. dry with materialThe mixture was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by the silica gel chromatography (hexane/ethyl acetate=7/3)

Sources & evidence

ORD record
ord-1140f4b97cbb42ddae246ca3e5d47519
Source dataset
uspto-grants-2009_02
Patent number
US07494989B2

Reaction notes

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