The invention relates to a
crystallization purification method, and relates to a
crystallization purification method of a
favipiravir key intermediate 3,6-difluoropyrazine-2-carbonitrile, and belongsto the field of
medicinal chemistry. The method comprises the following steps: mixing a crude product of 3, 6-difluoropyrazine-2-carbonitrile with ethyl tert-butyl
ether, stirring the materials, adding
column chromatography silica gel; heating to 50-65 DEG C, performing stirring decolorization for a period of time, performing
solid-liquid separation, cooling the resulting clarified solution, stirring and crystallizing for a period of time; then, performing
solid-liquid separation, and obtaining the product 3, 6-difluoropyrazine-2-carbonitrile; wherein the
mass ratio of the 3, 6-difluoropyrazine-2-carbonitrile crude product to the ethyl tert-butyl
ether is 1: 3-1: 15, wherein the
mass ratio of the 3, 6-difluoropyrazine-2-carbonitrile crude product to the
column chromatography silica gel is1: 1. 0.5 to 1: 5,
column chromatography silica gel is used as a decolorizing agent; ethyl tert-butyl
ether is used as a
crystallization solvent, crystallization conditions are controlled,
tar in the3, 6-difluoropyrazine-2-carbonitrile can be effectively removed, the content of impurities 6-chloro-3-fluoropyrazine-2-carbonitrile is reduced, the
crystallinity of the 3, 6-difluoropyrazine-2-carbonitrile is enhanced, the purity of the obtained product is high, operation is simple, and industrial production is facilitated.