Ethanol → Valproic Acid

HRID 2225957Notes

Reaction equation

HRID 2225957 reaction equation
CS(O)(=O)=O.[CH2:6]([C:9]([CH2:20][CH2:21][CH3:22])(C(OCC)=O)[C:10]([O:12]CC)=[O:11])[CH2:7][CH3:8].C(O)C>O>[C:10]([OH:12])(=[O:11])[CH:9]([CH2:20][CH2:21][CH3:22])[CH2:6][CH2:7][CH3:8]

Participants

5

Reactant 3

HCID 702EthanolHCID 6395Methanesulfonic AcidHCID 80168Diethyl dipropylmalonate

Product 1

HCID 3121Valproic AcidYield 123.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 38.6 ml of 70% methanesulfonic acid and 352.2 g of diethyl dipropylmalonate was heated to 135°-145° C. in a flask equipped with a distillation column packed with Raschig rings. After 1.5 hour, ethanol began to reflux in the distillation head. Ethanol was distilled as it formed and the pot temperature was maintained at 120°-145° C. by periodic addition of water to the pot. After 5 hours, additional ester (133 g) was added to the pot and the distillation of ethanol was continued. After 24 hours, the distillation of ethanol had ceased. The mixture then was cooled and treated with 50 ml of water. The layers were separated and the organic layer was washed with 100 ml of 5% sodium chloride solution to afford 257.6 g (90% yield) of valproic acid as a light brown liquid.

Workup

  1. temperaturewas heated to 135°-145° C. in a flask
  2. customequipped with a distillation column
  3. temperatureto reflux in the distillation head
  4. distillationEthanol was distilled as it
  5. customformed
  6. waitAfter 5 hours
  7. distillationthe distillation of ethanol
  8. waitAfter 24 hours
  9. distillationthe distillation of ethanol
  10. temperatureThe mixture then was cooled
  11. additiontreated with 50 ml of water
  12. customThe layers were separated
  13. washthe organic layer was washed with 100 ml of 5% sodium chloride solution

Sources & evidence

ORD record
ord-89a8afea4ec94f62b83039d77f1778e7
Source dataset
uspto-grants-1994_09
Patent number
US05344975

Reaction notes

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