Diflunisal → 1-(Ethoxycarbonyloxy)ethyl 5-(2,4-difluorophenyl)salicylate

HRID 1719725Notes

Reaction equation

HRID 1719725 reaction equation
[CH:1]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]([F:14])=[CH:11][C:12]=2[F:13])=[CH:5][C:4]([C:15]([OH:17])=[O:16])=[C:3]([OH:18])[CH:2]=1.[H-].[Na+].[C:21](=[O:29])([O:25][CH:26](Cl)[CH3:27])[O:22][CH2:23][CH3:24]>CN(C=O)C>[F:13][C:12]1[CH:11]=[C:10]([F:14])[CH:9]=[CH:8][C:7]=1[C:6]1[CH:5]=[C:4]([C:15]([O:17][CH:23]([O:22][C:21]([O:25][CH2:26][CH3:27])=[O:29])[CH3:24])=[O:16])[C:3]([OH:18])=[CH:2][CH:1]=1

Participants

5

Reactant 3

HCID 3059DiflunisalHCID 24758Sodium hydrideHCID 162095Carbonic acid, 1-chloroethyl ethyl ester

Product 1

HCID 134913951-(Ethoxycarbonyloxy)ethyl 5-(2,4-difluorophenyl)salicylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of diflunisal (5.0 g) in 40 ml DMF was added 0.8 g of sodium hydride (oil suspension containing 60% of NaH). The resultant mixture was stirred for 1.5 hours at room temperature before 3.0 ml of ethyl 1-chloroethyl carbonate was added dropwise. The reaction mixture was stirred at room temperature overnight and concentrated in vacuo. The concentrate was partitioned between ether/ethyl acetate and acidified water. The organic layer was separated and the aqueous layer was extracted again with ether. The organic layers were combined, washed well with water, dried over anhydrous sodium sulfate and concentrated to 6.6 g of crude product. After further purification by chromatography (eluted through 120 g of silica gel with hexane, and then 5% ethyl acetate in hexane), the product was crystallized from hexane to afford 3.71 g of 1-(ethoxycarbonyloxy)ethyl 5-(2,4-difluorophenyl)salicylate.

Workup

  1. additionwas added dropwise
  2. concentrationconcentrated in vacuo
  3. customThe concentrate was partitioned between ether/ethyl acetate
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted again with ether
  6. washwashed well with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated to 6.6 g of crude product
  9. customAfter further purification by chromatography (
  10. washeluted through 120 g of silica gel with hexane
  11. custom5% ethyl acetate in hexane), the product was crystallized from hexane

Sources & evidence

ORD record
ord-f86c552ff4b14b5cbed0245ed8dd00c3
Source dataset
uspto-grants-1985_09
Patent number
US04542158

Reaction notes

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