2-Fluorobenzoic acid → 2-Fluoro-benzoic acid 1-ethoxycarbonyl-2-oxo-2-phenyl-ethyl ester

HRID 1726376Notes

Reaction equation

HRID 1726376 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[H-].[Na+].[CH2:13]([O:15][C:16](=[O:27])[CH:17](Cl)[C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH3:14]>C1COCC1.C(O)C>[CH2:13]([O:15][C:16]([CH:17]([O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=1[F:1])[C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:27])[CH3:14]

Participants

6

Reactant 3

HCID 99352-Fluorobenzoic acidHCID 24758Sodium hydrideHCID 9855991Ethyl 2-chloro-3-oxo-3-phenylpropanoate

Product 1

HCID 690680262-Fluoro-benzoic acid 1-ethoxycarbonyl-2-oxo-2-phenyl-ethyl esterYield 38%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

2-Fluorobenzoic acid (6 g, 42.8 mmole) was dissolved in 300 mL of anhydrous THF and the resulting reaction solution was cooled to 0° C. To this solution was added sodium hydride (1.88 g of a 60% oil dispersion, 47.1 mmole). The reaction mixture was allowed to warm to room temperature over 1 h. The THF was removed by evaporation before addition of 2-chloro-3-oxo-3-phenyl-propionic acid ethyl ester (9.7 g, 42.8 mmole) in 250 mL of ethanol. Reaction solution was warmed at reflux for 24 h. The ethanol was removed by evaporation and the resulting product was dissolved in water and extracted with toluene. The toluene was washed with 2 N aqueous Na2CO3, and saturated NaCl. The resulting toluene layer was concentrated and purified by chromatography (5-8% ethyl acetate in hexanes gradient) providing 2-fluoro-benzoic acid 1-ethoxycarbonyl-2-oxo-2-phenyl-ethyl ester (Intermediate XVIIb, 5.3 g, 38% yield)

Workup

  1. customthe resulting reaction solution
  2. temperatureto warm to room temperature over 1 h
  3. customReaction solution
  4. temperaturewas warmed
  5. temperatureat reflux for 24 h
  6. customThe ethanol was removed by evaporation
  7. dissolutionthe resulting product was dissolved in water
  8. extractionextracted with toluene
  9. washThe toluene was washed with 2 N aqueous Na2CO3, and saturated NaCl
  10. concentrationThe resulting toluene layer was concentrated
  11. custompurified by chromatography (5-8% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-c52ee2c1cad144deb15e22063ccad917
Source dataset
uspto-grants-2009_02
Patent number
US07491821B2

Reaction notes

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