4-Chlorobenzaldehyde → 2-(4-Chloro-benzylidene)-3-methyl-succinic acid

HRID 238608

Reaction equation

HRID 238608 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1.C[O:13][C:14](=[O:22])[CH:15]([CH3:21])[CH2:16][C:17]([O:19]C)=[O:18].[OH-].[Na+]>C1(C)C=CC=CC=1.CO>[Cl:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[C:16]([CH:15]([CH3:21])[C:14]([OH:22])=[O:13])[C:17]([OH:19])=[O:18])=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 77264-ChlorobenzaldehydeHCID 14798Sodium HydroxideHCID 15350Butanedioic acid, 2-methyl-, 1,4-dimethyl esterHCID 24758Sodium hydride

Product 1

HCID 673042002-(4-Chloro-benzylidene)-3-methyl-succinic acidYield 26.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent2×

Procedure

After careful addition of absolute methanol (0.1 mL) to a suspension of sodium hydride (60% in mineral oil, 16 g, 0.40 mol) in anhydrous toluene (200 mL), a solution of 4-chloro-benzaldehyde (28 g, 0.20 mol) and 2-methyl-succinic acid dimethyl ester (48 g, 0.30 mol) in anhydrous toluene (100 mL) was added dropwise at room temperature under a stream of nitrogen. After being stirred at room temperature for 2 hours, the resulting mixture was diluted by adding 2 N sodium hydroxide (200 mL) dropwise, then heated to 80° C., and stirred at the same temperature for 2 hours. After being cooled to room temperature naturally, the aqueous layer was separated, washed with ethyl acetate (100 mL×3), then acidified with 2 N hydrochloric acid to pH 2, and extracted with ethyl acetate (150 mL×3). The combined organic layers were dried over sodium sulfate, and concentrated in vacuo. The residue was precipitated from ethyl acetate/petroleum ether (10:1) to give 2-(4-chloro-benzylidene)-3-methyl-succinic acid (13.4 g, 26%) as a yellow solid.

Workup

  1. additionthe resulting mixture was diluted
  2. temperatureheated to 80° C.
  3. stirringstirred at the same temperature for 2 hours
  4. temperatureAfter being cooled to room temperature naturally
  5. customthe aqueous layer was separated
  6. washwashed with ethyl acetate (100 mL×3)
  7. extractionextracted with ethyl acetate (150 mL×3)
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residue was precipitated from ethyl acetate/petroleum ether (10:1)

Sources & evidence

ORD record
ord-a0f2adc394ca490f87771b901d954ca3
Source dataset
uspto-grants-2014_02
Patent number
US08642629B2

Linked notes

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