反应详情

温度

27.5 °C

A 500-mL jacketed reactor equipped with a pH meter, temperature probe and metering addition funnel was charged with denatured ethanol (contained 5% 2-propanol, 30 mL) and water (150 mL). The reaction mixture was stirred while diethyl oxalacetate sodium salt (70 g, 0.33 mol) was added over 10 minutes. A solution of 25% aqueous NaOH (14 g, 56 mL, 0.35 mol) was metered into the stirring vortex over 1 h while maintaining the temperature in a range of 25 to 30 ° C. The reaction mixture was stirred for an additional 30 minutes at 30 ° C., and cyclopropanecarboximidamide monohydrochloride (32 wt % solution in water, 32 g, 0.267 mol) was added. A solution of 25% aqueous NaOH (31 g, 0.19 mol) was added at a temperature ranging from 30 to 35 ° C. over about 1 h so as to maintain the pH in the range of 10.5-11.5. Then the resulting orange mixture was gradually heated to 60 ° C. over a period of 1 h and held at the same temperature for additional 30 minutes. The reaction mixture was cooled to 45-50 ° C., and hydrochloric acid (37 wt. % in water, 50 mL, 0.60 mol) was added over 1 h at about 45 ° C. (CAUTION: foaming) until the pH reached to about 1.5. The reaction mixture was cooled to 5 ° C. and filtered. The resulting wet cake was washed with water (3×20 mL), suction-dried, and dried in a vacuum-oven at 70 ° C. for 16 h to afford 42 g (85% yield) of the title compound as a beige solid (97% purity by HPLC assay) decomposing at 235-236 ° C.

1. customequipped with a pH meter, temperature probe and metering addition funnel
2. additionwas added over 10 minutes
3. waitranging from 30 to 35 ° C. over about 1 h
4. temperatureso as to maintain the pH in the range of 10.5-11.5
5. temperatureThen the resulting orange mixture was gradually heated to 60 ° C. over a period of 1 h
6. waitheld at the same temperature for additional 30 minutes
7. temperatureThe reaction mixture was cooled to 45-50 ° C.
8. temperatureThe reaction mixture was cooled to 5 ° C.
9. filtrationfiltered
10. washThe resulting wet cake was washed with water (3×20 mL)
11. customsuction-dried
12. customdried in a vacuum-oven at 70 ° C. for 16 h