Ethanol → 3-Ethoxy-2,4,5-trifluorobenzoic acid

HRID 376024Notes

Reaction equation

HRID 376024 reaction equation
[F:1][C:2]1[C:3](F)=[C:4]([F:14])[C:5]([F:13])=[C:6]2C(=O)[O:10][C:8](=[O:9])[C:7]=12.O.[OH-].[Li+].[CH2:19]([OH:21])[CH3:20]>O>[CH2:19]([O:21][C:3]1[C:2]([F:1])=[C:7]([CH:6]=[C:5]([F:13])[C:4]=1[F:14])[C:8]([OH:10])=[O:9])[CH3:20]

Participants

5

Reactant 3

HCID 702EthanolHCID 69545Tetrafluorophthalic anhydrideHCID 168937Lithium hydroxide, monohydrate

Product 1

HCID 106326943-Ethoxy-2,4,5-trifluorobenzoic acidYield 77.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
140 °C

Procedure

4.4 g (20 mmol) of tetrafluorophthalic anhydride are dissolved in 3 g of water and 30 g of ethanol, 4.2 g of lithium hydroxide hydrate are added, and the mixture is heated at reflux for 48 hours. Then 50 g of water are added and an ethanol/water mixture (31.9 g) is distilled off until a head temperature of 100° C. is reached. Subsequently a pH of 0.6 is established by adding 19 g of 30% strength hydrochloric acid, and the mixture is extracted using a mixture of 20 g of 1,2-dichlorobenzene and 10 g of Hostarex A327. The organic phase is dried over MgSO4, heated at 140° C. for one hour until the evolution of gas comes to an end (decarboxylation) and then adjusted at 25° C. to a pH of 14 using 12.1 g of 35% strength sodium hydroxide solution. The mixture is extracted three times with in each case 50 g of dichloromethane, and the aqueous phase is adjusted to a pH of 0.7 by adding 9.4 g of 30% strength hydrochloric acid and extracted with MTBE. The mixture is dried over MgSO4 and filtered, and removal of the solvent leaves 3.4 g (15.5 mmol, corresponding to 77%) of yellowish 3-ethoxy-2,4,5-trifluorobenzoic acid (purity by GC>95%).

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux for 48 hours
  3. distillationan ethanol/water mixture (31.9 g) is distilled off until a head temperature of 100° C.
  4. additionby adding 19 g of 30% strength hydrochloric acid
  5. extractionthe mixture is extracted
  6. additiona mixture of 20 g of 1,2-dichlorobenzene and 10 g of Hostarex A327
  7. dry with materialThe organic phase is dried over MgSO4
  8. customadjusted at 25° C. to a pH of 14
  9. extractionThe mixture is extracted three times with in each case 50 g of dichloromethane
  10. additionby adding 9.4 g of 30% strength hydrochloric acid
  11. extractionextracted with MTBE
  12. dry with materialThe mixture is dried over MgSO4
  13. filtrationfiltered
  14. customremoval of the solvent

Sources & evidence

ORD record
ord-8a9413beaee14fc08321506db700bcde
Source dataset
uspto-grants-1996_01
Patent number
US05488152

Reaction notes

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