Reacción #61098

Ecuación de reacción

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

Rendimiento 35.9%

Disolventes

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otropartitioned between ethyl acetate and water
2. 2
   OtroThe organic layer was separated
3. 3
   Secadodried over sodium sulfate
4. 4
   Filtraciónfiltered
5. 5
   Concentraciónconcentrated in vacuo
6. 6
   OtroThe residue was purified by chromatography over silica gel
7. 7
   Lavadoeluted first with ethyl acetate
8. 8
   Lavadogradient eluted with dichloromethane containing from 0 to 10% methanol
9. 9
   OtroPrecipitation of the isolated product from dichloromethane with an excess of hexanes

Procedimiento

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%).

Fuente