Refinement technique of fluorometholone

Abstract

The invention relates to the field of refinement methods of compounds, and particularly relates to a refinement technique of fluorometholone. The refinement method is characterized by comprising the following particular technical steps of (1), dissolving 100g of fluorometholone crude product in 400mL to 500mL of one or several of amide organic solvents, agitating and heating an obtained first mixture to 80 to 90 DEG C, and maintaining the temperature for 0.5h; (2), slowly adding 1L to 2L of alcohol solvent, maintaining a temperature in an interval of 60 to 75 DEG C in an entire addition process, after the addition is completed, maintaining temperature for 0.5h, then decreasing the temperature to 0 to 5 DEG C, maintaining the second mixture at 0 to 5 DEG C to crystallize the second mixture for 12h; (3), filtering and drying an obtained third mixture to obtain 25g to 33g of similarly white crystal fluorometholone refined product. The mass concentration of the fluorometholone crude product in the step (1) is 97 to 98 percent. By using the refinement method, the impurity problem in the refinement of the fluorometholone is solved; not only is a related substance of the fluorometholone enabled to completely meet requirements in the British Pharmacopoeia BP2008 and the United States Pharmacopoeia USP36, that is, the purity is more than 99 percent, and a single impurity is less than 0.5 percent, but also a known single impurity can be guaranteed to be less than 0.15 percent, the total impurity can be guaranteed to be less than 0.1 percent; the great improvement is achieved compared with the requirements in the Pharmacopoeias.

Description

technical field [0001] The invention relates to the field of a compound refining process, in particular to a fluorometholone refining process. Background technique [0002] Fluorometholone is a very useful class of glucocorticoid drugs. Fluorometholone has a good anti-inflammatory effect and can be used on the skin, eyes and other parts, and is widely used in dermatitis, eczema, and inflammatory eye diseases. The literature AnnOphthalmol.1975, (1): 139-42 points out that the clinical study of patients using fluorometholone and dexamethasone in the eyes shows that fluorometholone has a smaller effect on intraocular pressure than dexamethasone. Fluorometholone has a good anti-inflammatory effect and has important applications in medicine, especially in ophthalmology. [0003] There are many synthetic routes of fluorometholone, such as patents US2864838, CN101397325A, Tetrahedron, 2009, 65, 8493-8496, but there are few reports on the refining method of fluorometholone. At pres...

AI Technical Summary

Problems solved by technology

[0005] In order to solve the problems existing in the fluorometholone recrystallization method proposed in the above-mentioned background technology, the present invention proposes a refining process of fluorometholone, which solves the impurity problem of fluorometholone, so that the related substances of fluorometholone not only fully comply with The requirements in the British Pharmacopoeia BP2008 and the United States Pharmacopoeia USP36, that is, the purity is greater than 99%, the single impurity is less than 0.5%, and it can ensure that the known single impurity is less than 0.15%, and the total impurity is less than 0.1%.