反应详情

4.14 g (4.55 mmol) of the compound from example 3A was dissolved in 90 ml tetrahydrofuran. 3.17 ml (22.8 mmol) triethylamine, 0.86 ml (22.8 mmol) formic acid and 0.526 g (0.455 mmol) tetrakis(triphenylphosphin)palladium(0) were added. The reaction mixture was stirred over night at room temperature. The reaction was diluted with approx. 100 ml water, and twice extracted with approx. 100 ml dichloromethane. The combined organic phases were extracted with brine, dried over sodium sulfate and concentrated to dryness under reduced pressure. The raw product was dissolved in dichloromethane and chromatographed over approx. 500 ml silica gel. Solvents used were dichloromethane, dichloromethane/methanol 20/1 and dichloromethane/methanol 1/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 2.62 g raw product of 94.5% purity. The product was further purified by preparative RP-HPLC on a C18 with a water/methanol gradient to yield 2.35 g (2.70 mmol, 59% of theory) pure product.

1. extractiontwice extracted with approx. 100 ml dichloromethane
2. extractionThe combined organic phases were extracted with brine
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated to dryness under reduced pressure
5. dissolutionThe raw product was dissolved in dichloromethane
6. customchromatographed over approx. 500 ml silica gel
7. concentrationconcentrated to dryness under reduced pressure
8. customThe product was further purified by preparative RP-HPLC on a C18 with a water/methanol gradient
9. customto yield 2.35 g (2.70 mmol, 59% of theory) pure product