C21 steroid 21 site acetylation process

Abstract

The invention discloses a C21 steroid 21 site acetylation process. C21 steroid is prednisolone, hydrocortisone, dexamethasone or betamethasone; the C21 steroid is subjected to acetylation with aceticanhydride; the acetylation of the C21 steroid with the acetic anhydride is carried out in a mixed solvent; an acetic acid alkali metal salt is adopted as a catalyst, and the reaction is carried out inthe presence of an inert gas; the mixed solvent is a mixed solvent of tetrahydrofuran and acetone; the weight ratio of the tetrahydrofuran to the acetone in the mixed solvent is (2-9):1. High-toxicity and high ammonia nitrogen pyridine and dimethylformamide are replaced by using the mixed solvent of tetrahydrofuran and acetone without ammonia nitrogen, no high ammonia nitrogen wastewater is generated, and environment pollution can be reduced.

Description

technical field [0001] The invention relates to the field of chemistry, in particular to a acetylation reaction process at position 21 of C21 steroids, and belongs to the technical field of chemical pharmacy. Background technique [0002] C21 steroid 21 acetylates such as prednisolone acetate, hydrocortisone acetate, dexamethasone acetate, betamethasone acetate, etc. are important adrenal glucocorticoid drugs, mainly used in the treatment of rheumatoid arthritis, Rheumatic fever, gout, bronchial asthma, allergic, non-infectious skin diseases and some proliferative skin diseases. It has very significant anti-inflammatory and immunosuppressive effects. The 21-position acetylation of C21 steroids is mainly produced by the reaction of C21 steroids with acetic anhydride, such as prednisolone, hydrocortisone, dexamethasone, betamethasone and acetic anhydride to prepare prednisolone acetate, Hydrocortisone acetate, dexamethasone acetate, betamethasone acetate. The traditional ac...

AI Technical Summary

Problems solved by technology

Although this method can also replace pyridine, the organic amine contains too much ammonia nitrogen, and the subsequent wastewater treatment costs are high and uneconomical

And the yield differs too much from the theoretical yield, so it is not suitable for industrialized production;

[0005] 3. The publication number is CN104710494A, which is a process developed by the applicant to replace pyridine to prepare hydrocortisone acetate and prednisolone acetate. It adopts acetylation reaction in dipolar aprotic solvent, dipolar aprotic solvent The representative solvent is dimethylformamide, which enters the wastewater after reaction, producing a large amount of wastewater containing ammonia and nitrogen. The cost of wastewater treatment is too high, which is still a major disadvantage in terms of environmental protection.