反应详情

温度

-40 °C

To a solution of 0.75 g of ethyl 4-[[2-oxo-4-(piperidin-4-yl)-piperazin-1-yl]acetyl]phenoxyacetate dihydrochloride synthesized according to the method described in WO962503 in 16 ml of methylene chloride was added 1.11 g of proton sponge under ice-cooling. After stirring for 5 minutes, the mixture was cooled to −40° C., and a solution of 0.322 g of 1-chloro-2-methylpropyl chloroformate in 2 ml of methylene chloride. After stirring for 45 minutes, the reaction mixture was diluted with ethyl acetate and water, and the organic layer was separated. The aqueous layer was extracted with ethyl acetate. The organic layer collected was washed with saturated aqueous saline, dried over sodium sulfate, and the solvent was removed by distillation. The residue was purified by chromatography on a silica gel column (methylene chloride:methanol=50:1-40:1) to give 0.624 g (74%) of ethyl 4-[[4-[1-(1-chloroethoxycarbonyl)piperidin-4-yl]-2-oxopiperazin-1-yl]acetyl]phenoxyacetate.

1. temperaturecooling
2. stirringAfter stirring for 45 minutes
3. customthe organic layer was separated
4. extractionThe aqueous layer was extracted with ethyl acetate
5. customThe organic layer collected
6. washwas washed with saturated aqueous saline
7. dry with materialdried over sodium sulfate
8. customthe solvent was removed by distillation
9. customThe residue was purified by chromatography on a silica gel column (methylene chloride:methanol=50:1-40:1)