反応 #61101

反応方程式

(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

溶媒

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   その他partitioned between ethyl acetate and water
2. 2
   その他The organic layer was separated
3. 3
   乾燥dried over sodium sulfate
4. 4
   ろ過filtered
5. 5
   濃縮concentrated in vacuo
6. 6
   その他The residue was purified by chromatography over silica gel gradient
7. 7
   洗浄eluted with 0-100% ethyl acetate in hexanes
8. 8
   その他the isolated material further purified by preparative thin layer chromatography
9. 9
   洗浄eluted with ethyl acetate
10. 10
    その他Precipitation of the isolated product from dichloromethane with an excess of hexanes

実験手順

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%).

出典