Reacción #976830

Ecuación de reacción

(E)-6-(4-chloro-2-fluorophenyl)-2,4-dioxo-hex-5-enoic acid ethyl ester

ammonium acetate

→

(2Z,5E)-2-amino-6-(4-chloro-2-fluorophenyl)-4-oxo-hexa-2,5-dienoic acid ethyl ester

Rendimiento 70.0%

Disolventes

EtOH

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaheated
2. 2
   Temperaturato reflux for 1 h
3. 3
   OtroThe solvent was removed under reduced pressure
4. 4
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2 (200 mL)
5. 5
   Lavadowashed with saturated aqueous sodium carbonate (Na2CO3, 100 mL)
6. 6
   SecadoAfter drying over MgSO4, silica gel (50 g)
7. 7
   workup.ADDITIONwas added
8. 8
   Otrothe solvent was removed
9. 9
   LavadoThe residue was washed with 20% ethyl acetate (EtOAc)/hexanes (300 mL)
10. 10
    Otroto give
11. 11
    Otroafter 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. 12
    LavadoFurther washing of the silica gel with 40% EtOAc/hexanes (400 mL)

Procedimiento

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%).

Fuente