Stage #1: hydrazinecarboxylic acid methyl ester; Triethyl orthoacetate; aniline With toluene-4-sulfonic acid In isopropyl methanesulfonate for 24h; Heating / reflux;
Stage #2: With sodium methylate In isopropyl methanesulfonate at 20℃; for 72h; Heating / reflux;
Stage #3: With acetic acid In isopropyl methanesulfonate; water
a.Aniline (74.5 g, 0.8 mol), methyl carbazate (79.26 g, 0.88 mol), p-toluenesulfonic acid(2g), and triethyl orthoacetate (161.4 mL, 0.88 mol) were combined in IMS (800 mL) and heated at reflux for 1 day. The solution was cooled to room temperature and NaOCH3 (43.22 g, 0.8 mol) was added. This was then heated at reflux for 3 days, and then the solvent was removed. Water was added (1.2 L), and the pH was adjusted to 5 with acetic acid. The precipitate was collected, washed with water and dried to afford the target compound (68 g).
With sulfuric acid; nitric acid at 0 - 20℃; for 0.5h;
The product from step a (26 g, 0.1484 mol) was added in portions to H2SO4 (169 mL) chilled to 2 - 5 0C. After the material had dissolved, nitric acid (165 mL) was added slowly. Upon completion of the addition, the reaction was stirred for 10 minutes in the ice bath, and then 20 minutes at room temperature. The reaction mixture was poured cautiously onto 600 g of ice diluted with some water. The precipitate was filtered and recrystallized from IMS to give the desired material (17.23 g).