反应详情

温度

55 °C

To a stirred suspension of hydroxylamine hydrochloride (1.56573 g, 0.0223062 mol) in anhydrous methanol (6.0 mL) at rt was added 4.37 M of sodium methoxide in methanol (7.64 mL). The reaction mixture was heated at 55° C. for 5 min, cooled to rt, then to 0° C. Filtration afforded a clear solution assumed to be ca. 1.50 M in methanol. To a stirred solution of methyl(3R,4S)-1-[(E)-(cyanoimino)(piperidin-1-yl)methyl]-4-[4-(4-cyano-2-methylphenyl)piperazin-1-yl]carbonylpiperidine-3-carboxylate (53.30 mg, 0.0001054 mol) in anhydrous methanol (1.110 mL, 0.02740 mol) at rt was added the above 1.50 M of hydroxylamine in methanol (1.40 mL). The reaction mixture was stirred at rt for 2 h. LCMS showed the reaction was done. The reaction was quenched with saturated aqueous NH4Cl, extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC with 5-95% MeCN/H2O to give the product. MS (ESI): (M+H)+=507.

1. temperaturecooled to rt
2. customto 0° C
3. filtrationFiltration
4. customafforded a clear solution
5. customThe reaction was quenched with saturated aqueous NH4Cl
6. extractionextracted with EtOAc (2×)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified by reverse phase HPLC with 5-95% MeCN/H2O
12. customto give the product