反应详情

Methyl trans-4-({2-[(t-butoxycarbonyl)amino]ethyl}amino)-cyclohexanecarboxylate (785 mg) obtained in Reference Example 71 (1) is dissolved in chloroform (8 ml), and thereto are added triethylamine (1.82 ml) and chloroacetyl chloride (249 μl) under ice-cooling. The mixture is then stirred at room temperature for 2 hours. The reaction solution is cooled with ice again, and chloroacetyl chloride (62 μl) is supplied thereto. The mixture is stirred at room temperature for 1 hour. To the reaction solution, saturated aqueous sodium hydrogen carbonate solution is poured and the mixture is extracted with chloroform. The organic layer is washed with water and saturated brine successively, dried over sodium sulfate and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=2/1, followed by 1/1) to give methyl trans-4-[{2-[(t-butoxycarbonyl)amino]ethyl}-(chloroacetyl)amino]cyclohexanecarboxylate (568 mg).

1. temperaturecooling
2. temperatureThe reaction solution is cooled with ice again
3. stirringThe mixture is stirred at room temperature for 1 hour
4. extractionthe mixture is extracted with chloroform
5. washThe organic layer is washed with water and saturated brine successively
6. dry with materialdried over sodium sulfate
7. customevaporated
8. customto remove the solvent under reduced pressure
9. customThe resulting residue is purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=2/1, followed by 1/1)