반응 #61098

반응 방정식

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

수율 35.9%

용매

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   기타partitioned between ethyl acetate and water
2. 2
   기타The organic layer was separated
3. 3
   건조dried over sodium sulfate
4. 4
   여과filtered
5. 5
   농축concentrated in vacuo
6. 6
   기타The residue was purified by chromatography over silica gel
7. 7
   세척eluted first with ethyl acetate
8. 8
   세척gradient eluted with dichloromethane containing from 0 to 10% methanol
9. 9
   기타Precipitation of the isolated product from dichloromethane with an excess of hexanes

실험 절차

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%).

출처