反应详情

A 100 mL round bottomed flask is charged with semicarbazide hydrochloride (2 g, 17.93 mmol), ethyl pyruvate (11.8 mL) and sodium ethanoate (2.97 g). Then water (9 mL) is added. The mixture is stirred at room temperature for 90 minutes, then it is filtered and solids are washed with more water. White solid is dried under vacuum in an oven (40° C.) overnight. 2.66 g of ethyl-2-(carbamoylhydrazono)-propanoate is obtained pure. Phosphoryl chloride (3.28 mL) is added dropwise to dimethylformamide (7.13 mL) at 0° C. Cooling bath is removed to reach room temperature Then, the mixture is heated to 40° C. and ethyl-2-(carbamoylhydrazono)propanoate previously obtained (2.66 g, 15.36 mmol) is added in several portions over 15-20 min (gas evolution during the addition). When internal temperature is 55° C., heating bath is removed so internal temperature is maintained in the range 60-70° C. Then, the mixture is heated to 80° C. Almost no more gas evolution is observed once the reaction is stabilized at 80° C. The resulting suspension is stirred at 80° C. for 2 h. Reaction mixture is poured over ice/water (30 mL) mixture and stirred to get a suspension. 50% solution of sodium hydroxide is added dropwise until pH 10 is reached. The solution is stirred at 50° C. for 5 min. Solution is then cooled with ice/water bath and 35% aqueous solution of hydrochloric acid is added until pH 7. The mixture is extracted with ethyl acetate. Organic layer is decanted, dried over magnesium sulfate and solvent is evaporated under reduced pressure. The residue is triturated with hexane and some drops of dichloromethane to give 1.6 g of ethyl 4-formyl-1H-pyrazole-3-carboxylate that is used in the next step without further purification. MS (m/z): 169 (M+1).

1. filtrationit is filtered
2. washsolids are washed with more water
3. customWhite solid is dried under vacuum in an oven (40° C.) overnight