Malonic Acid → 2-Acetyl-6-fluorobenzoic acid

HRID 1872487Notes

Reaction equation

HRID 1872487 reaction equation
[F:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:4]2[C:5]([O:7][C:8](=[O:9])[C:3]=12)=[O:6].[C:13](O)(=O)CC(O)=O.Cl.O>C(N(CC)CC)C>[C:5]([C:4]1[CH:10]=[CH:11][CH:12]=[C:2]([F:1])[C:3]=1[C:8]([OH:7])=[O:9])(=[O:6])[CH3:13]

Participants

5

Reactant 3

HCID 867Malonic AcidHCID 695513-Fluorophthalic anhydrideHCID 21885828Hydrate;hydrochloride

Product 1

HCID 152786862-Acetyl-6-fluorobenzoic acid

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

9 g of 3-fluorophthalic anhydride and 6.8 g of malonic acid are mixed in 80 ml of triethylamine and heated in an oil bath at 71-72° until evolution of gas ceases. The reaction mixture is mixed with 50 ml of 10% HCl/H2O and extracted with ether. The ether is evaporated off and the resulting black oil chromatographed on a column using 1 l of 20% of ethylacetate/hexane followed by 1 l of 30% ethylacetate/hexane to yield first the 3fluoro-isomer followed by the desired 6-fluoro isomer; m.p. 76-81.5°.

Workup

  1. temperatureheated in an oil bath at 71-72° until evolution of gas ceases
  2. extractionextracted with ether
  3. customThe ether is evaporated off
  4. customthe resulting black oil chromatographed on a column
  5. customto yield first the 3fluoro-isomer

Sources & evidence

ORD record
ord-5d21d2cf0e744fc3ae5f774b918b48b9
Source dataset
uspto-grants-2000_08
Patent number
US06110868

Reaction notes

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