反应详情

温度

130 °C

Ethyl 2-aminonicotinate (121, Example 4) (367.3 mg, 2.238 mmol) was added to 3-phenoxyphenylacetyl chloride (1.0 g, 4.4 mmol) in a 10 mL round-bottom flask. A stir bar and pyridine (2.0 mL, distilled) were added and the mixture heated to reflux (130° C., oil bath) under nitrogen with stirring for 3 h, then cooled to room temperature. The reaction mixture was quenched with water (10 mL) and extracted with chloroform (3×15 mL). The combined organic extracts were washed with sat. NaHCO3 (3×10 mL) and water (3×10 mL), dried (MgSO4), and rota-evaporated to dryness, leaving a dark residue. This residue was chromatographed on silica gel (24 g, Mallinckrodt, grade 62; mesh 60-200) and eluted with hexanes-EtOAc (1:4, 300 mL). The desired fractions were collected (Rf =0.52) and rota-evaporated to dryness, leaving an orange oil. This oil eventually precipitated out as a wet orange mass. Crystallization from ethanol afforded the title compound as yellow flakes, 224 mg (26.5%), mp 90°-1° C.; 1H NMR (CDCl3): δ1.39 (t, J=6.8, 3, CH3CH2), 3.83 (s, 2, benzylic), 4.35 (q, J=6.8, 2, CH3CH2O), 7.10 (m, 9, phenyl), 8.29 (dd, J1 =1.5, J2 =7.8, 1, py), 8.59 (dd, J1 =1.5, J2 =4.8, 1, py), 10.81 (s, 1, NH); IR (KBr): 3441, 3168, 1723, 1668, 1660, 1549, 1490, 1436, 1409, 1307, 1246, 1211, 1143, 1027, 980, 775, 700; HPLC: 100%; LRMS: 377 (10), 376 (M+, 45), 211 (15), 210 (100), 183 (10), 167 (15), 166 (25), 147 (35), 121 (10), 94 (35), 89 (30), 77 (15), 51 (10), 39 (10); HRMS Calcd: 376.1423. Found: 376.1419.

1. temperaturethe mixture heated
2. temperaturecooled to room temperature
3. customThe reaction mixture was quenched with water (10 mL)
4. extractionextracted with chloroform (3×15 mL)
5. washThe combined organic extracts were washed with sat. NaHCO3 (3×10 mL) and water (3×10 mL)
6. dry with materialdried (MgSO4)
7. customrota-evaporated to dryness
8. customleaving a dark residue
9. customThis residue was chromatographed on silica gel (24 g, Mallinckrodt, grade 62; mesh 60-200)
10. washeluted with hexanes-EtOAc (1:4, 300 mL)
11. customThe desired fractions were collected (Rf =0.52)
12. customrota-evaporated to dryness
13. customleaving an orange oil
14. customThis oil eventually precipitated out as a wet orange mass
15. customCrystallization from ethanol