反应详情

温度

130 °C

To a mixture of ethyl 2-amino-5-chloronicotinate (143, Example 18) (344.9 mg, 1.719 mmol) in pyridine (2.0 mL, distilled) in a 10 mL round-bottom flask with stirring was added a solution of 3-phenoxyphenylacetyl chloride (812.5 mg, 3.293 mmol) in dry CH2Cl2 (2.0 mL). The mixture was gradually heated to reflux (130° C., oil bath), over which time the CH2Cl2 was allowed to evaporate. The resulting solution was refluxed for 3.5 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 water (3×10 mL), dried (MgSO4), and rota-evaporated to dryness, leaving a dark green liquid. This liquid was chromatographed on silica gel (24 g, Mallinckrodt, grade 62, mesh 60-200) and eluted with hexanes-EtOAc (1:4, 250 mL). The desired fractions were collected (Rf =0.83) and rota-evaporated to dryness, leaving a green oil. This oil eventually precipitated out as a wet green mass. Crystallization from ethanol afforded the title compound as a light brown flakes, 114 mg (16.1%), mp 103°-4° C.; 1H NMR (CDCl3): δ1.39 (t, J=7.2, 3, CH3CH2), 3.88 (s, 2, benzylic), 4.35 (q, J=7.2, 2, CH3CH2O), 7.10 (m, 9, phenyl), 8.24 (d, J=2.4, 1, py), 8.52 (d, J=2.4, 1, py), 10.70 (d, J=2.4, 1, NH); IR (KBr): 3434, 3155, 2925, 1722, 1659, 1401, 1252, 1205, 1102, 775, 700; HPLC: 99%; LRMS: 410 (M+, 40), 211 (35), 210 (100), 200 (35), 183 (30), 181 (40), 128 (15), 89 (50), 77 (20), 51 (15); HRMS Calcd: 410. 1033. Found: 410.1026.

1. temperatureThe mixture was gradually heated
2. customto evaporate
3. temperatureThe resulting solution was refluxed for 3.5 h
4. temperaturecooled to room temperature
5. customThe reaction mixture was quenched with water (10 mL)
6. extractionextracted with chloroform (3×15 mL)
7. washThe combined organic extracts were washed with water (3×10 mL)
8. dry with materialdried (MgSO4)
9. customrota-evaporated to dryness
10. customleaving a dark green liquid
11. customThis liquid was chromatographed on silica gel (24 g, Mallinckrodt, grade 62, mesh 60-200)
12. washeluted with hexanes-EtOAc (1:4, 250 mL)
13. customThe desired fractions were collected (Rf =0.83)
14. customrota-evaporated to dryness
15. customleaving a green oil
16. customThis oil eventually precipitated out as a wet green mass
17. customCrystallization from ethanol