반응 #61101

반응 방정식

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

diphosgene

diisopropylethylamine

→

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

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 gradient
7. 7
   세척eluted with 0-100% ethyl acetate in hexanes
8. 8
   기타the isolated material further purified by preparative thin layer chromatography
9. 9
   세척eluted with ethyl acetate
10. 10
    기타Precipitation of the isolated product from dichloromethane with an excess of hexanes

실험 절차

Crude (2S,3S)-2-{(R)-2-amino-2-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-acetylamino}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide (≈0.19 mmol) was dissolved in tetrahydrofuran (10 mL) that contained diisopropylethylamine (160 μL, 122 mg, 0.94 mmol) and was transferred via cannula to a solution of diphosgene (16 μL, 26 mg, 0.13 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 gradient eluted with 0-100% ethyl acetate in hexanes and the isolated material further purified by preparative thin layer chromatography using silica gel eluted with ethyl acetate. Precipitation of the isolated product from dichloromethane with an excess of hexanes gave (2S,3S)-2-{4-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide as an off white solid (32 mg, 29%).

출처