反应详情

An aluminum foil covered flask containing a solution of 4-[(R)-1-(3,5-dichloro-4-fluoro-phenyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[1,2-a]imidazol-3-ylmethyl]-benzonitrile (48.8 g, 117.5 mmol) in CH2Cl2 (900 mL) was partially submerged in an ice water bath. To this solution was added a solid mixture of N-iodosuccinimide (29.1 g, 129 mmol) and pyridinium p-toluenesulfonate (2.95 g, 11.7 mmol) in four separate portions over a 30 min period. The reaction was allowed to stir in the thawing ice bath for 1 h and then the bath was removed. Stirring was continued overnight. Saturated aqueous Na2S2O3 (300 mL) was added to the reaction and the mixture was transferred to a separatory funnel using CH2Cl2 (200 mL) and water (1 L). The layers were separated and the aqueous layer was further extracted with CH2Cl2 (2×500 mL) and EtOAc (500 mL). The combined organic layers were dried over MgSO4 and concentrated in-vacuo to give a yellow oil. This oil was purified by flash chromatography on silica gel (0-2.5% EtOAc/toluene) to give 52 g of the title compound as a white solid, m/z 541.3 [M+H]+.

1. customwas partially submerged in an ice water bath
2. additionTo this solution was added
3. customseparate portions over a 30 min period
4. customthe bath was removed
5. stirringStirring
6. waitwas continued overnight
7. additionSaturated aqueous Na2S2O3 (300 mL) was added to the reaction
8. customthe mixture was transferred to a separatory funnel
9. customThe layers were separated
10. extractionthe aqueous layer was further extracted with CH2Cl2 (2×500 mL) and EtOAc (500 mL)
11. dry with materialThe combined organic layers were dried over MgSO4
12. concentrationconcentrated in-vacuo
13. customto give a yellow oil
14. customThis oil was purified by flash chromatography on silica gel (0-2.5% EtOAc/toluene)