反应详情

To a vial charged with 1-(2′-amino-7-(5-chloro-2-fluorophenyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-3-yloxy)propan-2-one (0.140 g, 0.308 mmol), p-toluenesulfonic acid (0.159 g, 0.925 mmol), and 4 Angstrom molecular seives was added 3 mL toluene. The resulting mixture was treated with ethylene glycol (0.022 mL, 0.401 mmol) and was heated to reflux. After stirring for 10 hours, copper(ii) sulfate (0.059 g, 0.617 mmol) was added followed by an additional portion of ethylene glycol (0.022 mL, 0.401 mmol). The reaction mixture was heated to reflux for an additional 4 hours before being allowed to cool to RT. The mixture was poured into saturated NaHCO3 (25 mL) solution and extracted with EtOAc (3×25 mL). The organics were washed with brine, dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography gave 7-(5-chloro-2-fluorophenyl)-3-((2-methyl-1,3-dioxolan-2-yl)methoxy)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine. MS m/z=498.0 [M+H].

1. temperaturewas heated to reflux
2. temperatureThe reaction mixture was heated
3. temperatureto reflux for an additional 4 hours
4. extractionextracted with EtOAc (3×25 mL)
5. washThe organics were washed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. customPurification of the crude residue by column chromatography