반응 #1127701

반응 방정식

aluminum

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

N-iodosuccinimide

pyridinium p-toluenesulfonate

→

title compound

수율 81.8%

4-[(R)-1-(3,5-Dichloro-4-fluoro-phenyl)-5-iodo-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[1,2-a]imidazol-3-ylmethyl]-benzonitrile

수율 81.8%

용매

CH2Cl2

반응 조건

후처리

1. 1
   기타was partially submerged in an ice water bath
2. 2
   workup.ADDITIONTo this solution was added
3. 3
   기타separate portions over a 30 min period
4. 4
   기타the bath was removed
5. 5
   workup.STIRRINGStirring
6. 6
   workup.WAITwas continued overnight
7. 7
   workup.ADDITIONSaturated aqueous Na2S2O3 (300 mL) was added to the reaction
8. 8
   기타the mixture was transferred to a separatory funnel
9. 9
   기타The layers were separated
10. 10
    추출the aqueous layer was further extracted with CH2Cl2 (2×500 mL) and EtOAc (500 mL)
11. 11
    건조The combined organic layers were dried over MgSO4
12. 12
    농축concentrated in vacuo
13. 13
    기타to give a yellow oil
14. 14
    기타This oil was purified by flash chromatography on silica gel (0-2.5% EtOAc/toluene)

실험 절차

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]+.

출처