Reaktion #89765

Reaktionsgleichung

hydroxylamine hydrochloride

sodium methoxide

methyl(3R,4S)-1-[(E)-(cyanoimino)(piperidin-1-yl)methyl]-4-[4-(4-cyano-2-methylphenyl)piperazin-1-yl]carbonylpiperidine-3-carboxylate

hydroxylamine

→

(3R,4S)-1-[(E)-(cyanoimino)(piperidin-1-yl)methyl]-4-[4-(4-cyano-2-methylphenyl)piperazin-1-yl]carbonyl-N-hydroxypiperidine-3-carboxamide

Lösungsmittel

methanol

methanol

methanol

methanol

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled to rt
2. 2
   Sonstigeto 0° C
3. 3
   FiltrationFiltration
4. 4
   Sonstigeafforded a clear solution
5. 5
   SonstigeThe reaction was quenched with saturated aqueous NH4Cl
6. 6
   Extraktionextracted with EtOAc (2×)
7. 7
   WaschenThe combined organic layers were washed with brine
8. 8
   Trocknendried over sodium sulfate
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated in vacuo
11. 11
    SonstigeThe residue was purified by reverse phase HPLC with 5-95% MeCN/H2O
12. 12
    Sonstigeto give the product

Vorschrift

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.

Quelle