反应详情

温度

0 °C

Add a solution of oxazole (0.5 mL, 7.24 mmol) in deoxygenated THF (50 mL) at −78° C. to 1.6 M n-butyllithium in hexane (5 mL, 7.96 mmol). After stirring for 30 minutes, add 1M zinc chloride in Et2O (22 mL, 21.7 mmol) and warm the reaction mixture to 0° C. for 2 hours. To the reaction mixture, add first a solution of 1′-(5-iodo-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one (3.2 g, 7.18 mmol), then the palladium catalyst which is prepared by treating a suspension of (Ph3P)2PdCl2 (0.25 g, 0.36 mmol) in deoxygenated THF (50 mL) with 1.6 M n-butyllithium in hexane (0.45 mL, 0.72 mmol). Reflux the reaction mixture for 20 hours. After cooling to ambient temperature, dilute the mixture with EtOAc (50 mL), and wash with water (50 mL) and saturated aqueous NaCl (50 mL). Dry the organic portion over Na2SO4, filter and concentrate. Purify by flash column chromatography (5% MeOH—CH2Cl2) to obtain 1′-(5-oxazol-2-yl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one as a white solid.

1. additionby treating
2. temperatureReflux the reaction mixture for 20 hours
3. temperatureAfter cooling to ambient temperature
4. washwash with water (50 mL) and saturated aqueous NaCl (50 mL)
5. dry with materialDry the organic portion over Na2SO4
6. filtrationfilter
7. concentrationconcentrate
8. customPurify by flash column chromatography (5% MeOH—CH2Cl2)