The invention discloses a preparation method of diflucolone or diflucolone
valerate, which comprises the following steps: in an
inert protective
atmosphere, carrying out reduction reaction on flumethasone and a
reducing agent in a
solvent to obtain the diflucolone, the preparation method comprises the following steps: in an
inert protective
atmosphere, carrying out
acylation reaction on difluorocolone and an
acylation reagent in a
solvent in the presence of a base catalyst to obtain the difluorocolone
valerate. The specific
solvent is adopted in the reduction reaction, the problems that in the prior art, reaction by-products are large,
raw material reaction is not thorough, the yield is low, and the production cost is high are solved, the product purity and the overall yield are obviously improved, and the production cost is reduced. According to the method, inorganic alkali and
acetone are used as a solvent in the
acylation reaction, the solvent can be recycled after post-treatment, the method is environment-friendly, 11-site hydroxyl is prevented from being acylated under the acylation condition, byproducts are effectively controlled, and the purity and yield of the product are improved.