反应详情

A two liter Buchi reactor was charged with 42.7 g (131.4 mmol, 1.0 equiv.) of 4-[(2,4-dinitro-phenyl)-methyl-carbamoyl]-butyric acid methyl ester, 20 g of 10% palladium on carbon (4.7% weight ratio palladium vs. starting material), and 650 mL of methanol at ambient temperature. The resulting mixture was subjected to hydrogenation at 40 psi overnight, about 18 hours. HPLC indicated that the reaction was complete in about 6-7 hours (HPLC Method B). The reaction mixture was filtered through a thin layer of Celite® 540. To the filtrate was added 11 mL of concentrated hydrochloric acid (1.0 equiv.). The resulting mixture was stirred under reflux for 3.5 hours. Approximately a half amount of solvent was removed under reduced pressure. Tert-butyl methyl ether (MTBE, 900 mL) was added with vigorous stirring. The precipitate was collected by filtration and washed with a mixture of MeOH-MTBE (1:10). The product was dried in an over at 60° C. overnight under vacuum to afford a tan solid (36.8 g, 99% yield) with a purity of 99 Area % by HPLC analysis (HPLC Method B).

1. customat ambient temperature
2. customwas subjected to hydrogenation at 40 psi overnight, about 18 hours
3. filtrationThe reaction mixture was filtered through a thin layer of Celite® 540
4. temperatureunder reflux for 3.5 hours
5. customApproximately a half amount of solvent was removed under reduced pressure
6. additionTert-butyl methyl ether (MTBE, 900 mL) was added with vigorous stirring
7. filtrationThe precipitate was collected by filtration
8. washwashed with a mixture of MeOH-MTBE (1:10)
9. customThe product was dried in an over at 60° C. overnight under vacuum