Acetic Acid → 5-Fluoro-2-methyl-1H-indene-3-acetic acid

HRID 377741Notes

Reaction equation

HRID 377741 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH:7]([CH3:12])[C:8]2=O)=[CH:4][CH:3]=1.C([CH2:15][C:16]([OH:18])=[O:17])#N.C(O)(=O)C.C([O-])(=O)C.[NH4+]>C1(C)C=CC=CC=1.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5](=[CH:4][CH:3]=1)[CH2:6][C:7]([CH3:12])=[C:8]2[CH2:15][C:16]([OH:18])=[O:17]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 9740Cyanoacetic acidHCID 517165Ammonium AcetateHCID 114465226-Fluoro-2-methylindan-1-one

Product 1

HCID 30156085-Fluoro-2-methyl-1H-indene-3-acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 6-fluoro-2-methylindanone (18.4 g, 0.112 mol), cyanoacetic acid (10.5 g, 0.123 mol), acetic acid (6.6 g), and ammonium acetate (1.7 g) in dry toluene (15.5 ml) is refluxed for 21 hours, as the liberated water is collected in a Dean Stark trap. The mixture is evaporated to dryness, and the residue is dissolved in hot ethanol (60 ml) and 2.2 N aqueous potassium hydroxide solution (14 ml). 85% KOH (22 g) in water (150 ml) is added, and the mixture is refluxed for 13 hours under nitrogen. The ethanol is removed in vacuo, and water (500 ml) is added. The aqueous solution is washed well with ether and is boiled with charcoal, and is filtered. The aqueous filtrate is acidified to pH 2 with 50% cold hydrochloric acid. The precipitate yields the title compound, 5-fluoro-2-methylinden-3-yl acetic acid (m.p. 164-166° C.).

Workup

  1. customis collected in a Dean Stark trap
  2. customThe mixture is evaporated to dryness
  3. dissolutionthe residue is dissolved in hot ethanol (60 ml)
  4. addition85% KOH (22 g) in water (150 ml) is added
  5. temperaturethe mixture is refluxed for 13 hours under nitrogen
  6. customThe ethanol is removed in vacuo, and water (500 ml)
  7. additionis added
  8. washThe aqueous solution is washed well with ether
  9. filtrationis filtered

Sources & evidence

ORD record
ord-2d11f934f52d44e3999efec7f04a6968
Source dataset
uspto-grants-2000_02
Patent number
US06028116

Reaction notes

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