反应 #61098

反应方程式

diphosgene

(2S,3S)-2-{(R)-2-amino-2-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-acetylamino}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

diisopropylethylamine

→

(2S,3S)-2-{2,5-dioxo-4-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-imidazolidin-1-yl}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

收率 35.9%

溶剂

tetrahydrofuran

tetrahydrofuran

反应条件

后处理

1. 1
   其他partitioned between ethyl acetate and water
2. 2
   其他The organic layer was separated
3. 3
   干燥dried over sodium sulfate
4. 4
   过滤filtered
5. 5
   浓缩concentrated in vacuo
6. 6
   其他The residue was purified by chromatography over silica gel
7. 7
   洗涤eluted first with ethyl acetate
8. 8
   洗涤gradient eluted with dichloromethane containing from 0 to 10% methanol
9. 9
   其他Precipitation of the isolated product from dichloromethane with an excess of hexanes

实验过程

Crude (2S,3S)-2-{(R)-2-amino-2-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-acetylamino}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide (≈0.16 mmol) was dissolved in tetrahydrofuran (10 mL) that contained diisopropylethylamine (142 μL, 105 mg, 0.81 mmol) and was transferred via cannula to a solution of diphosgene (14 μL, 23 mg, 0.12 mmol) in tetrahydrofuran (15 mL) at 0° C. The reaction mixture was stirred for 20 minutes and then partitioned between ethyl acetate and water. The organic layer was separated and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography over silica gel eluted first with ethyl acetate and then gradient eluted with dichloromethane containing from 0 to 10% methanol. Precipitation of the isolated product from dichloromethane with an excess of hexanes gave (2S,3S)-2-{2,5-dioxo-4-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-imidazolidin-1-yl}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide as a white solid (26 mg, 27%).

来源