Methyl 2-(6-chloro-2-methoxypyridin-3-yl)-3-cyano-2-methylpropanoate → 3-(6-Chloro-2-methoxypyridin-3-yl)-3-methylpyrrolidin-2-one
Reaktionsgleichung
[Cl:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]([CH3:18])([CH2:15][C:16]#[N:17])[C:11](OC)=[O:12])=[CH:4][CH:3]=1.[H][H]>N.CO.[Ni]>[Cl:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]2([CH3:18])[CH2:15][CH2:16][NH:17][C:11]2=[O:12])=[CH:4][CH:3]=1Komponenten
Edukt 2
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 3
Versuchsvorschrift
A Parr bottle was charged with a solution of methyl 2-(6-chloro-2-methoxypyridin-3-yl)-3-cyano-2-methylpropanoate (2.35 g, 8.73 mmol) in 7 M ammonia in MeOH and a slurry of Raney nickel (5.82 g, 67.9 mmol, washed 2× with water and 4× with MeOH) in 7 M ammonia in MeOH (99 mL total to charge both reagents, 690 mmol). The reaction was shaken with hydrogen (30 psi) for 6 h. The catalyst was filtered through a pad of Celite® under nitrogen rinsing with EtOH. The filtrate was then concentrated to give a light green oil/foam. Purification by silica gel column chromatography (80 g RediSep Gold column, 30-100% Ethyl acetate/Heptanes) provided 3-(6-chloro-2-methoxypyridin-3-yl)-3-methylpyrrolidin-2-one (1.9 g, 90%) as a white solid. 1H NMR (600 MHz, CDCl3) δ: 1.56 (s, 3H), 2.08 (ddd, 1H), 2.58 (dt, 1H), 3.37 (td, 1H), 3.40-3.46 (m, 1H), 3.97 (s, 3H), 5.86 (br. s., 1H), 6.89 (d, 1H), 7.61 (d, 1H); MS (ES+)(M+H) 241.
Aufarbeitung
- filtrationThe catalyst was filtered through a pad of Celite® under nitrogen rinsing with EtOH
- concentrationThe filtrate was then concentrated
- customto give a light green oil/foam
- customPurification by silica gel column chromatography (80 g RediSep Gold column, 30-100% Ethyl acetate/Heptanes)
Quellen und Nachweise
- ORD-Eintrag
- ord-5b79f1fcd35243b4a95b75fb8c2afb49
- Quelldatensatz
- uspto-grants-2016_03
- Patentnummer
- US09278953B2
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