Reaktion #71001

Reaktionsgleichung

sodium ethoxide

3-chloro-4-(2-fluoro-4-(1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)-picolinamide

3-chloro-4-(4-(4-chloro-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)-2-fluorophenoxy)picolinamide

Sodium hydride

→

desired product

Ausbeute 88.0%

3-Chloro-4-(4-(4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)-2-fluorophenoxy)picolinamide

Ausbeute 88.0%

Lösungsmittel

THF

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for 1 h at rt
2. 2
   EinengenThe reaction mixture was concentrated in vacuo
3. 3
   workup.DISSOLUTIONsaturated aqueous sodium bicarbonate solution, and water (to dissolve any precipitated salts)
4. 4
   SonstigeThis mixture was sonicated
5. 5
   workup.STIRRINGstirred until the remaining solid
6. 6
   FiltrationThis powder was filtered off

Vorschrift

Sodium hydride (1.89 g, 47.2 mmol, 60% dispersion in mineral oil, Aldrich) was added slowly to a solution of ethanol (77 mL, Aldrich>99.5% 200 proof) and THF (77 mL) under N2 and the resulting mixture was stirred at rt for 5 min. The sodium ethoxide solution was then added to a mixture of 3-chloro-4-(2-fluoro-4-(1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)-picolinamide and 3-chloro-4-(4-(4-chloro-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)-2-fluorophenoxy)picolinamide (22.6 g, ˜36.3 mmol) and stirred for 1 h at rt. The reaction mixture was concentrated in vacuo. The resulting crude solid was suspended in ethyl acetate, saturated aqueous sodium bicarbonate solution, and water (to dissolve any precipitated salts). This mixture was sonicated and stirred until the remaining solid became a filterable powder. This powder was filtered off to yield 17.2 g (88%) of the desired product as a pale yellow solid. The layers of the remaining filtrate were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting solid was triturated with ethyl acetate, sonicated, and filtered to give an additional 3.02 g of the desired product as a pale brown solid. 1H NMR (CD3OD) δ 8.34 (d, 1H, J=5.6 Hz), 7.94 (dd, 1H, J=12.4, 2.4 Hz), 7.80 (d, 1H, J=8 Hz), 7.48-7.46 (m, 3H), 7.31-7.28 (m, 3H), 6.86 (d, 1H, J=5.6 Hz), 6.61 (d, 1H, J=7.2 Hz), 4.34 (q, 2H, J=7.2 Hz), 1.45 (t, 3H, J=7.2 Hz); MS(ESI+) m/z 541.11 (M+H)+.

Quelle