Methyl 2-(6-chloro-2-methoxypyridin-3-yl)-3-cyano-2-methylpropanoate → 3-(6-Chloro-2-methoxypyridin-3-yl)-3-methylpyrrolidin-2-one

Participants

Reaction Steps

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.

Provenance & Evidence