反应详情

Formamidine acetate (500 g) and methyl 3-oxopentanoate (500 g) were added to a solution of sodium methoxide (500 g) in methanol (4 L) at 20° C. and the mixture stirred for 15 hours. Water (1 L) and acetic acid (500 ml) were added to give a pH of 7. The solvent was removed by evaporation under reduced pressure and the aqueous residue was diluted with water (1 L) and extracted with methyl ethyl ketone (4×2.5 L). The organic phases were combined and concentrated by evaporation under reduced pressure to give an orange syrup. The syrup was dissolved in ethyl acetate (1 L) and the solution stirred for 15 hours to give a solid. The solid was collected by filtration, washed with ethyl acetate (200 ml, at 10° C.) and dried at 50° C. under reduced pressure to provide the title compound (183 g). After concentrating the mother liquors under reduced pressure, diethyl ether (3 L) was added to provide a solid. This was solid was collected by filtration, washed with tert-butyl methyl ether (200 ml) and dried at 50° C. under reduced pressure to provide a second crop of the title compound (195 g). The total yield of the title compound was approximately 79%.

1. customto give a pH of 7
2. customThe solvent was removed by evaporation under reduced pressure
3. additionthe aqueous residue was diluted with water (1 L)
4. extractionextracted with methyl ethyl ketone (4×2.5 L)
5. concentrationconcentrated by evaporation under reduced pressure
6. customto give an orange syrup
7. stirringthe solution stirred for 15 hours
8. customto give a solid
9. filtrationThe solid was collected by filtration
10. washwashed with ethyl acetate (200 ml, at 10° C.)
11. customdried at 50° C. under reduced pressure