反应详情

温度

130 °C

Phenylacetyl chloride (0.21 mL, d=1.169, 1.6 mmol) was added to ethyl 2-amino-5-chloronicotinate (143) (159.6 mg, 0.7956 mmol) in a 10 mL round-bottom flask. A stir bar and pyridine (1.0 mL, distilled) were added. The mixture was heated to reflux (130° C., oil bath) with stirring under nitrogen. The resulting solution was refluxed for 1 h, then cooled to room temperature. The reaction mixture was quenched with water (5 mL) and extracted with chloroform (3×10 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 an orange liquid. This liquid was chromatographed on silica gel (30 g, Mallinckrodt, grade 62, mesh 60-200) and eluded with hexanes-EtOAc (1:4, 250 mL). The desired fractions were collected (Rf =0.79) and rota-evaporated to dryness, leaving an orange solid. Crystallization from ethanol afforded the title compound as yellow needles, 110 mg (43.6%), mp 113.5°-114° C.; 1H NMR (CDCl3): δ1.38 (t, J=7.2, 3, CH3CH2), 3.90 (s, 2, benzylic), 4.34 (q, J=7.2, 2, CH3CH2O), 7.38 (m, 5, phenyl), 8.22 (d, J=2.4, 1, py), 8.54 (d, J=2.4, 1, py), 10.64 (s, 1, NH); IR (KBr): 3427, 3196, 1743, 1640, 1600, 1409, 1272, 1218, 1136, 1096, 796; HPLC: 100%; LRMS: 318 (M+, 25), 202 (20), 201 (10), 200 (60), 183 (15), 181 (40), 154 (10), 128 (10), 118 (100 ), 91 (80), 65 (25), 39 (10); HRMS Calcd: 318.0771. Found: 318.0772.

1. temperatureThe mixture was heated
2. temperatureThe resulting solution was refluxed for 1 h
3. temperaturecooled to room temperature
4. customThe reaction mixture was quenched with water (5 mL)
5. extractionextracted with chloroform (3×10 mL)
6. washThe combined organic extracts were washed with sat. NaHCO3 (3×10 mL) and water (3×10 mL)
7. dry with materialdried (MgSO4)
8. customrota-evaporated to dryness
9. customleaving an orange liquid
10. customThis liquid was chromatographed on silica gel (30 g, Mallinckrodt, grade 62, mesh 60-200)
11. customThe desired fractions were collected (Rf =0.79)
12. customrota-evaporated to dryness
13. customleaving an orange solid
14. customCrystallization from ethanol