Réaction #61101

Équation de réaction

(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

Solvants

tetrahydrofuran

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Autrepartitioned between ethyl acetate and water
2. 2
   AutreThe organic layer was separated
3. 3
   Séchagedried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated in vacuo
6. 6
   AutreThe residue was purified by chromatography over silica gel gradient
7. 7
   Lavageeluted with 0-100% ethyl acetate in hexanes
8. 8
   Autrethe isolated material further purified by preparative thin layer chromatography
9. 9
   Lavageeluted with ethyl acetate
10. 10
    AutrePrecipitation of the isolated product from dichloromethane with an excess of hexanes

Mode opératoire

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%).

Source