反应详情

The generated mixture of N-benzyl-N-(2-ethoxycarbonyl-ethyl)-malonamic acid ethyl ester and N-benzyl-N-(2-ethoxycarbonyl-ethyl)-malonamic acid methyl ester was treated with sodium methoxide (2.97 mL, 13.0 mmol, 25% solution) in toluene at reflux for 18 hours. The cooled reaction mixture was acidified with 10% sulfuric acid and concentrated under vacuum. The resulting residue was dissolved in DCM and washed with water and brine, then dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel (gradient: 0 to 2% methanol in DCM) to afford 2.09 g (68%) of 1-benzyl-2,4-dioxo-piperidine-3-carboxylic acid methyl ester. 1H NMR (400 MHz, CDCl3) δ: 7.29 (m, 5H), 4.70 (s, 1H), 4.64 (s, 2H), 3.93 (s, 3H), 3.34 (t, 2H), 2.59 (t, 2H).

1. temperatureat reflux for 18 hours
2. customThe cooled reaction mixture
3. concentrationconcentrated under vacuum
4. dissolutionThe resulting residue was dissolved in DCM
5. washwashed with water and brine
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated under vacuum
8. customThe resulting residue was purified by column chromatography on silica gel (gradient: 0 to 2% methanol in DCM)