反应详情

To a solution of (−)-(1R,3R)-(3-azido-cyclopentyloxy)-tert-butyl-dimethyl-silane (540 mg, 2.24 mmol) (from Example 27c supra) in ethanol (30 mL) was added platinum oxide (51 mg, 0.22 mmol) (Aldrich) and the mixture was hydrogenated under 1 atmosphere of hydrogen overnight. The mixture was then filtered, the solids were washed with tetrahydrofuran (approximately 25 mL) and the combined filtrate was concentrated to a residue that was dissolved in dioxane (50 mL). To that solution was added triethylamine (620 μL, 450 mg, 4.48 mmol) (Aldrich) and ethyl 4-chloro-2-methylthio-5-pyrimidinecarboxylate (520 mg, 2.24 mmol) (Aldrich) and the mixture was stirred at reflux for 1 hour. The reaction mixture was then cooled and partitioned between ethyl acetate and water. The ethyl acetate layer was collected, dried over sodium sulfate and concentrated to a residue that was purified by silica gel column chromatography with a 0–20% ethyl acetate in hexanes gradient to give (+)-(1R,3R)-4-[3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester as a colorless viscous oil. (Yield 710 mg, 77%).

1. filtrationThe mixture was then filtered
2. washthe solids were washed with tetrahydrofuran (approximately 25 mL)
3. concentrationthe combined filtrate was concentrated to a residue that
4. dissolutionwas dissolved in dioxane (50 mL)
5. temperatureat reflux for 1 hour
6. temperatureThe reaction mixture was then cooled
7. custompartitioned between ethyl acetate and water
8. customThe ethyl acetate layer was collected
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated to a residue that
11. customwas purified by silica gel column chromatography with a 0–20% ethyl acetate in hexanes gradient