Water → Ethyl 4-(4-chloro-3-fluorophenyl)-4-oxobutanoate

HRID 2356765Notes

Reaction equation

HRID 2356765 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[F:10].[C-]#N.[Na+].[C:14]([O:18][CH2:19][CH3:20])(=[O:17])[CH:15]=[CH2:16].O>CN(C)C=O>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6](=[O:7])[CH2:16][CH2:15][C:14]([O:18][CH2:19][CH3:20])=[O:17])=[CH:4][C:3]=1[F:10]

Participants

6

Reactant 4

HCID 962WaterHCID 8821Ethyl AcrylateHCID 8929Sodium CyanideHCID 27249854-Chloro-3-Fluorobenzaldehyde

Product 1

HCID 24727751Ethyl 4-(4-chloro-3-fluorophenyl)-4-oxobutanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under argon atmosphere, to a solution of 4-chloro-3-fluoro-benzaldehyde (10 g) in N,N-dimethylformamide (50 ml) was added sodium cyanide (620 mg) at room temperature, and the mixture was stirred at the same temperature for 3 hours. Then, to the mixture was added dropwise a solution of ethyl acrylate (5.2 ml) in N,N-dimethylformamide (25 ml), and the resulting mixture was stirred at the room temperature for 3 hours. The reaction mixture was poured into water and extracted with diethyl ether. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane:ethyl acetate=20:1) to obtain ethyl 4-(4-chloro-3-fluorophenyl)-4-oxobutyrate (9.4 g) as pale yellowish powder.

Workup

  1. stirringthe resulting mixture was stirred at the room temperature for 3 hours
  2. extractionextracted with diethyl ether
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (solvent: hexane:ethyl acetate=20:1)

Sources & evidence

ORD record
ord-1bff6aff966f41ff8e7087dd95c4d335
Source dataset
uspto-grants-2010_07
Patent number
US07759373B2

Reaction notes

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