反应详情

温度

75 °C

To 1H-pyrazole-1-carboximidamide hydrochloride, 8-a, (44.22 g, 299 mmol) in EtOH (500 mL) was added sodium methoxide (102 mL, 448 mmol, 25 wt % in MeOH) and diethyl ethoxymethylenemalonate (61.0 mL, 299 mmol, 99%). The reaction was heated for about 40 min at 75° C. and then cooled slightly (to 71° C.) before adding potassium hydroxide (33.5 g, 597) in water (125 mL). The reaction was heated to 75° C. again for 1 h. During this time an additional portion of EtOH (100 mL) was added to improve mixing. The reaction was cooled to 40° C. before adding aq. HCl (81.3 mL, 991 mmol, 37%) in portions. The reaction aged for 1 h 40 min and then Et2O (180 mL) was added. The solids were filtered and rinsed with EtOH, Et2O and then hexane. The solid was then suspended in aq. HCl (300 mL, 0.67 M), filtered and washed with aq. HCl (300 mL, 1 M), 2:1 Et2O:EtOH (350 mL), 1:1 Et2O:EtOH (200 mL), Et2O (150 mL) and hexane (150 mL) to afford the title compound, 8-b. HPLC/MS: 207.2 (M+1); Rt=0.61 min.

1. temperaturecooled slightly (to 71° C.)
2. temperatureThe reaction was heated to 75° C. again for 1 h
3. additionto improve mixing
4. temperatureThe reaction was cooled to 40° C.
5. customThe reaction aged for 1 h 40 min
6. filtrationThe solids were filtered
7. washrinsed with EtOH, Et2O
8. filtrationfiltered
9. washwashed with aq. HCl (300 mL, 1 M), 2:1 Et2O