Hydrochloric Acid → Ethyl 4-(4-fluorophenyl)-2,4-dioxobutanoate

HRID 920704Notes

Reaction equation

HRID 920704 reaction equation
[O-]CC.[Na+].[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:14])[CH3:13])=[CH:8][CH:7]=1.[C:15](OCC)(=[O:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17].Cl>C(O)C>[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:14])[CH2:13][C:15](=[O:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7268Diethyl OxalateHCID 98284'-FluoroacetophenoneHCID 2723922Sodium ethoxide

Product 1

HCID 596593Ethyl 4-(4-fluorophenyl)-2,4-dioxobutanoateYield 70%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of sodium ethoxide (351 mL, 21% in ethanol, 1629 mmol) was added 1-(4-fluorophenyl) ethanone (150 g, 1086 mmol) in ethanol (100 mL) at 0° C. under a nitrogen atmosphere and the resulting reaction mixture was stirred at RT for 10 min Diethyl oxalate (156 mL, 1140 mmol) in ethanol (100 mL) was added and reaction was allowed to stir at RT for 12 h. Reaction mixture was cooled to 0° C. and acidified with 1.5 N HCl and the solid was filtered and the filtrate was diluted with water and extracted with DCM (3×750 mL). The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to afford Intermediate 1A (180 g, 70%) which was taken to next step without further purification. MS(ES): m/z=237 [M−H]+; 1H NMR (300 MHz, CDCl3) δ ppm 15.2 (bs, 1H), 8.00-8.09 (m, 2H), 7.15-7.25 (m, 2H), 7.05 (s, 1H), 4.42 (q, J=7.15 Hz, 2H), 1.43 (t, J=7.15 Hz, 3H).

Workup

  1. customthe resulting reaction mixture
  2. additionwas added
  3. customreaction
  4. customReaction mixture
  5. temperaturewas cooled to 0° C.
  6. filtrationthe solid was filtered
  7. additionthe filtrate was diluted with water
  8. extractionextracted with DCM (3×750 mL)
  9. washThe combined organic layer was washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-5315bda967b842ecb48042f2cc30b2b5
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

Loading…