反応 #1994300

反応方程式

(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

収率 70.0%

溶媒

EtOH

反応条件

後処理

1. 1
   温度heated
2. 2
   温度to reflux for 1 h
3. 3
   その他The solvent was removed under reduced pressure
4. 4
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2 (200 mL)
5. 5
   洗浄washed with saturated aqueous sodium carbonate (Na2CO3, 100 mL)
6. 6
   乾燥After drying over MgSO4, silica gel (50 g)
7. 7
   workup.ADDITIONwas added
8. 8
   その他the solvent was removed
9. 9
   洗浄The residue was washed with 20% ethyl acetate (EtOAc)/hexanes (300 mL)
10. 10
    その他to give
11. 11
    その他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
12. 12
    洗浄Further washing of the silica gel with 40% EtOAc/hexanes (400 mL)

実験手順

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%).

出典