反応 #89765

反応方程式

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

溶媒

methanol

methanol

methanol

methanol

methanol

反応条件

後処理

1. 1
   温度cooled to rt
2. 2
   その他to 0° C
3. 3
   ろ過Filtration
4. 4
   その他afforded a clear solution
5. 5
   その他The reaction was quenched with saturated aqueous NH4Cl
6. 6
   抽出extracted with EtOAc (2×)
7. 7
   洗浄The combined organic layers were washed with brine
8. 8
   乾燥dried over sodium sulfate
9. 9
   ろ過filtered
10. 10
    濃縮concentrated in vacuo
11. 11
    その他The residue was purified by reverse phase HPLC with 5-95% MeCN/H2O
12. 12
    その他to give the product

実験手順

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.

出典