Potassium Hydroxide → 3-[3-(Trifluoromethoxy)phenyl]propanoic acid

HRID 1275112Notes

Reaction equation

HRID 1275112 reaction equation
FC(F)(F)OC1C=C2C(=CC=1)C(=O)CC2.[F:16][C:17]([F:32])([F:31])[O:18][C:19]1[CH:20]=[C:21]([CH2:25][CH2:26][C:27]([O:29]C)=[O:28])[CH:22]=[CH:23][CH:24]=1.[OH-].[K+]>C(O)C.O>[F:16][C:17]([F:31])([F:32])[O:18][C:19]1[CH:20]=[C:21]([CH2:25][CH2:26][C:27]([OH:29])=[O:28])[CH:22]=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 22119021HCID 22119021, compoundHCID 221190265-(Trifluoromethoxy)-2,3-dihydro-1H-inden-1-one

Product 1

HCID 27772883-[3-(Trifluoromethoxy)phenyl]propanoic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

5-Trifluoromethoxyindan-1-one: 9.37 g of methyl 3-(3-trifluoromethoxyphenyl)propionate are dissolved in 50 ml of ethanol with 25 ml of water. 3.74 g of potassium hydroxide are added and the mixture is refluxed for 45 minutes. The cooled solution is concentrated, the residue is treated with 25 ml of water, and conc. hydrochloric acid is added with stirring until the pH is 1. The aqueous reaction mixture is extracted twice by shaking with 75 ml of dichloromethane in each case. The organic phase is washed with water, dried over magnesium sulfate, concentrated and dried in vacuo. 3-(3-trifluoromethoxy-phenyl) propionic acid is obtained as a colorless oil. 6.24 g of the acid are dissolved in 40 ml of toluene, and the solution is treated with 2.1 ml of thionyl chloride and refluxed for 1 hour. The cooled reaction mixture is concentrated, and the residue is taken up in 5 ml of toluene and concentrated again. 3-(3-Trifluoromethoxyphenyl)propionyl chloride is obtained, which is dissolved in 30 ml of dichloromethane without further purification and added dropwise at 0-5° C. with stirring in the course of 15 minutes to a suspension of 5.49 g of anhydrous aluminum trichloride in 40 ml of dichloromethane. The reaction mixture is stirred at 0° C. for one hour and then added to 40 ml of ice water. The organic phase is separated off and the aqueous phase is again extracted by shaking with 40 ml of dichloromethane. The combined organic phases are washed with 40 ml of satd. sodium hydrogencarbonate solution and water, dried over magnesium sulfate, concentrated in vacuo and, for purification, purified by chromatography on silica gel using toluene/ethyl acetate 20/1. 5-Trifluoromethoxyindan-1-one is obtained as a pale yellow oil.

Workup

  1. temperaturethe mixture is refluxed for 45 minutes
  2. concentrationThe cooled solution is concentrated
  3. additionthe residue is treated with 25 ml of water, and conc. hydrochloric acid
  4. additionis added
  5. extractionThe aqueous reaction mixture is extracted twice
  6. stirringby shaking with 75 ml of dichloromethane in each case
  7. washThe organic phase is washed with water
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customdried in vacuo

Sources & evidence

ORD record
ord-52a8720efc0e41d6ad76fea02b21f113
Source dataset
uspto-grants-2000_12
Patent number
US06159996

Reaction notes

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