تفاعل #1080225

معادلة التفاعل

ethyl 4-[[2-oxo-4-(piperidin-4-yl)-piperazin-1-yl]acetyl]phenoxyacetate dihydrochloride

proton sponge

1-chloro-2-methylpropyl chloroformate

→

ethyl 4-[[4-[1-(1-chloroethoxycarbonyl)piperidin-4-yl]-2-oxopiperazin-1-yl]acetyl]phenoxyacetate

المردود 77.7%

المذيبات

methylene chloride

ethyl acetate

water

methylene chloride

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooling
2. 2
   workup.STIRRINGAfter stirring for 45 minutes
3. 3
   أخرىthe organic layer was separated
4. 4
   استخلاصThe aqueous layer was extracted with ethyl acetate
5. 5
   أخرىThe organic layer collected
6. 6
   غسيلwas washed with saturated aqueous saline
7. 7
   تجفيفdried over sodium sulfate
8. 8
   أخرىthe solvent was removed by distillation
9. 9
   أخرىThe residue was purified by chromatography on a silica gel column (methylene chloride:methanol=50:1-40:1)

الإجراء التجريبي

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.

المصدر