反应详情

温度

60 °C

4.5 g N-(4-Cyano-1-dimethylamino-piperidin-4-yl)-N-hydroxy-2-(2,4,6-trimethyl-phenyl)-acetamide (from Step 3) is dissolved in 60 ml methanol. Then, 6.4 g concentrated sulfuric acid is added slowly. The mixture is heated to 60° C. for 2 days, then cooled to ambient temperature, and the solvent evaporated. The residue is partitioned with water and ethyl acetate, the organic layer is separated, washed with brine, dried over sodium sulfate, and the solvent is evaporated. The residue is purified by chromatography on silica gel, with ethyl acetate containing 7.5% triethylamine as a solvent. Thus, 1.35 g 1-Dimethylamino-4-{hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester is obtained. 1H-NMR (CDCl3): 7.90 ppm (s, broad, 1H), 6.84 ppm (s, 2H), 3.86 ppm (s, 2H), 3.71 ppm (s, 3H), 2.80 ppm (m, 2H), 2.70 ppm (m, 2H), 2.53 ppm (m, 2H), 2.40 ppm (s, 6H), 2.23 ppm (s, 3H), 2.22 ppm (s, 6H), 2.15 ppm (m, 2H).

1. temperaturecooled to ambient temperature
2. customthe solvent evaporated
3. customThe residue is partitioned with water and ethyl acetate
4. customthe organic layer is separated
5. washwashed with brine
6. dry with materialdried over sodium sulfate
7. customthe solvent is evaporated
8. customThe residue is purified by chromatography on silica gel, with ethyl acetate containing 7.5% triethylamine as a solvent