反应详情

Compound 78 (970 mg, 3.42 mmol) was dissolved in DCM (50 mL) and trimethyl silyl chloride (1.08 mL, 8.54 mmol) and tert-butyl nitrite (1.02 mL, 8.54 mmol) were added. The reaction mixture was stirred at rt for 60 h. The reaction was quenched with saturated aqueous sodium hydrogen carbonate (50 mL) and extracted with DCM (2×50 mL). The combined organic phases were dried (MgSO4), filtered and solvent removed in vacuo. The crude residue was suspended in toluene (50 mL), diethyl isopropylamine (1.49 mL) and phosphorus oxychloride (5 mL) were added. The resulting mixture was heated under reflux for 3 hours and then poured into ice water with vigorous stirring. The resulting solution was neutralized with sodium hydrogen carbonate and extracted with ethanol (3×100 mL). The combined organic phases were concentrated in vacuo and the residue purified by column chromatography (Biotage SP1, 100% DCM→10% MeOH-DCM) and trituration with EtOAc to afford the title compound (270 mg, 26%) as a pale brown solid. LCMS, Rt=3.03 min (MeOH-FA), m/z 304.

1. customThe reaction was quenched with saturated aqueous sodium hydrogen carbonate (50 mL)
2. extractionextracted with DCM (2×50 mL)
3. dry with materialThe combined organic phases were dried (MgSO4)
4. filtrationfiltered
5. customsolvent removed in vacuo
6. additiondiethyl isopropylamine (1.49 mL) and phosphorus oxychloride (5 mL) were added
7. temperatureThe resulting mixture was heated
8. temperatureunder reflux for 3 hours
9. additionpoured into ice water with vigorous stirring
10. extractionextracted with ethanol (3×100 mL)
11. concentrationThe combined organic phases were concentrated in vacuo
12. customthe residue purified by column chromatography (Biotage SP1, 100% DCM→10% MeOH-DCM) and trituration with EtOAc