Triethyl phosphonoacetate → Ethyl 3-[4-(trifluoromethyl)phenyl]propanoate

HRID 1977553Notes

Reaction equation

HRID 1977553 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.[H][H].[F:19][C:20]([F:30])([F:29])[C:21]1[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=1>C(COC)OC.O>[CH2:15]([O:14][C:12](=[O:13])[CH2:11][CH2:25][C:24]1[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:29])[F:30])=[CH:28][CH:27]=1)[CH3:16]

Participants

7

Reactant 4

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 679964-(Trifluoromethyl)benzaldehydeHCID 178418361HCID 178418361, compound

Product 1

HCID 11858695Ethyl 3-[4-(trifluoromethyl)phenyl]propanoateYield 57.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent3×

Conditions

Temperature
10 °C

Procedure

Dimethoxyethane 700 ml was added to 60% sodium hydride 24.8 g (620 mmol), the mixture was stirred at room temperature while a solution of ethyl diethylphosphonoacetate 139 g (620 mmol) in dimethoxyethane (100 ml) was added dropwise. After the generation of hydrogen gas was stopped, the solution was cooled to 10° C., and a solution of 4-trifluoromethylbenzaldehyde 100 g (574 mmol) in dimethoxyethane (100 ml) was added dropwise keeping the liquid temperature below 25° C. After addition, the mixture was stirred for 30 minutes, the reactant was added to water one liter, and the product was extracted with diethylether. The extract was washed with a sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: heptane/ethyl acetate=3/1). Such obtained purified material was hydrogenated in the presence of 5% palladium carbon as a catalyst in ethanol 300 ml. The catalyst was filtered off, the solvent was distilled off at reduced pressure to obtain 3-(4-trifluoromethylphenyl)propionic acid ethylester 81.0 g (329 mmol). The yield was 57.3% from 4-trifluoro methylbenzaldehyde.

Workup

  1. additionwas added dropwise
  2. customthe liquid temperature below 25° C
  3. additionAfter addition
  4. extractionthe product was extracted with diethylether
  5. washThe extract was washed with a sodium chloride aqueous solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluent: heptane/ethyl acetate=3/1)
  9. customSuch obtained
  10. custompurified material
  11. filtrationThe catalyst was filtered off
  12. distillationthe solvent was distilled off at reduced pressure

Sources & evidence

ORD record
ord-a96f4f14a69b471e96469e84b77d2aad
Source dataset
uspto-grants-2001_05
Patent number
US06235355B1

Reaction notes

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