Toluene → 4-(2,4-difluorophenyl)pent-4-enoic Acid

HRID 512801Notes

Reaction equation

HRID 512801 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=O)[CH2:10][CH2:11][C:12]([OH:14])=[O:13].[C:16]1(C)C=CC=CC=1.[I-].CP(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+]>O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[CH2:16])[CH2:10][CH2:11][C:12]([OH:14])=[O:13]

Participants

6

Reactant 4

HCID 1140TolueneHCID 27740813-(2,4-Difluorobenzoyl)propionic AcidHCID 23676156Sodium t-butoxideHCID 178503021HCID 178503021, compound

Product 1

HCID 111173524-(2,4-difluorophenyl)pent-4-enoic Acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
52.5 °C

Procedure

To a mixture of 4-(2,4-difluorophenyl)-4-oxobutanoic acid (100 g) and toluene (1000 ml), added methyl triphenylphosphine iodide (377.5 g) and sodium tertiary butoxide (183 g) at 25-30° C. Heated the reaction mixture to 50-55° C. and stirred for 6-8 hours at the same temperature. After completion of the reaction, cooled the reaction mixture to 25-30° C. Water was added to the reaction mixture and both organic and aqueous layers were separated. pH of aqueous layer was adjusted to 11 using 50% hydrochloric acid. Extracted the aqueous layer with toluene and washed the aqueous layer with dichloromethane. pH of the aqueous layer was further adjusted to 2.5 using 50% HCl and the reaction mixture was stirred for 45 minutes. Filtered the obtained solid, washed with water and then dried to get the title compound. Cyclohexane (500 ml) was added to the obtained solid and heated to 45-50° C. Carbon (10 g) was added to the reaction mixture and stirred for 15 minutes. Filtered the reaction mixture and washed with hot cyclohexane. Distilled off half of the solvent under reduced pressure. Cooled the reaction mixture to 10-15° C. and stirred for 60 minutes at the same temperature. Filtered the solid and washed with chilled cyclohexane and dried to get the title compound. Yield: 65.75 g

Workup

  1. customAfter completion of the reaction
  2. temperaturecooled the reaction mixture to 25-30° C
  3. customboth organic and aqueous layers were separated
  4. extractionExtracted the aqueous layer with toluene
  5. washwashed the aqueous layer with dichloromethane
  6. stirringthe reaction mixture was stirred for 45 minutes
  7. filtrationFiltered the obtained solid
  8. washwashed with water
  9. customdried

Sources & evidence

ORD record
ord-52d0ffe9d15b42e2a5f6fc83d6e83be8
Source dataset
uspto-grants-2015_08
Patent number
US09102664B2

Reaction notes

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