Ammonium Acetate → HCID 59612108, compound

HRID 889648Notes

Reaction equation

HRID 889648 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[C:5](=O)[CH2:6][C:7](=[O:18])/[CH:8]=[CH:9]/[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=1[F:17])[CH3:2].C([O-])(=O)C.[NH4+:25]>CCO>[CH2:1]([O:3][C:4](=[O:20])/[C:5](/[NH2:25])=[CH:6]/[C:7](=[O:18])/[CH:8]=[CH:9]/[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=1[F:17])[CH3:2]

Participants

4

Reactant 2

HCID 517165Ammonium AcetateHCID 59612092HCID 59612092, compound

Product 1

HCID 59612108HCID 59612108, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of (E)-6-(4-chloro-2-fluorophenyl)-2,4-dioxo-hex-5-enoic acid ethyl ester (3; 15.0 g, 0.05 mol) and ammonium acetate (7.7 g, 0.1 mol) in EtOH (100 mL) was stirred and heated to reflux for 1 h. The solvent was removed under reduced pressure, and the residue was dissolved in CH2Cl2 (200 mL) and washed with saturated aqueous sodium carbonate (Na2CO3, 100 mL). After drying over MgSO4, silica gel (50 g) was added and the solvent was removed. The residue was washed with 20% ethyl acetate (EtOAc)/hexanes (300 mL) to give after solvent removal (2Z,5E)-2-amino-6-(4-chloro-2-fluorophenyl)-4-oxo-hexa-2,5-dienoic acid ethyl ester (7; 6.1 g, 41%) as a light orange solid: mp 102-103° C.; 1H NMR (400 MHz, CDCl3) δ 9.4 (br s, 1H), 7.62 (d, J=15.9 Hz, 1H), 7.52 (t, J=8.5 Hz, 1H), 7.49 (d, J=8.3 Hz, 1H), 7.19-7.08 (m, 2H), 6.87 (d, J=15.9 Hz, 1H), 6.14 (s, 1H), 6.05 (br s, 1H), 4.37 (q, J=7.1 Hz, 2H), 1.39 (t, J=7.1 Hz, 3H); HRMS-ESI (m/z): calcd for C14H13ClFNO3, 297.056. found, 297.056. Further washing of the silica gel with 40% EtOAc/hexanes (400 mL) gave more (2Z,5E)-2-amino-6-(4-chloro-2-fluorophenyl)-4-oxo-hexa-2,5-dienoic acid ethyl ester (7; 8.8 g of 70% pure by 1H NMR spectroscopy) for a total of 12.2 g (82%).

Workup

  1. temperatureheated
  2. temperatureto reflux for 1 h
  3. customThe solvent was removed under reduced pressure
  4. dissolutionthe residue was dissolved in CH2Cl2 (200 mL)
  5. washwashed with saturated aqueous sodium carbonate (Na2CO3, 100 mL)
  6. dry with materialAfter drying over MgSO4, silica gel (50 g)
  7. additionwas added
  8. customthe solvent was removed
  9. washThe residue was washed with 20% ethyl acetate (EtOAc)/hexanes (300 mL)
  10. customto give
  11. customafter solvent removal (2Z,5E)-2-amino-6-(4-chloro-2-fluorophenyl)-4-oxo-hexa-2,5-dienoic acid ethyl ester (7; 6.1 g, 41%) as a light orange solid
  12. washFurther washing of the silica gel with 40% EtOAc/hexanes (400 mL)

Sources & evidence

ORD record
ord-b5cd363cfcd441efab47429dd5cb9e69
Source dataset
uspto-grants-2012_08
Patent number
US08252938B2

Reaction notes

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