- Preparation method of rocuronium bromide intermediate and rocuronium bromide
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The invention discloses a preparation method of a rocuronium bromide intermediate and rocuronium bromide. According to the method, (2beta,3alpha,5alpha,16beta,17beta)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)androstane-3,17-diol is used as an initial raw material, and is subjected to selective acetylation with glacial acetic acid under the action of a condensing agent to obtain (2beta,3alpha,5alpha,16beta,17beta)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)androstane-3,17-diol-17-acetate, and then (2beta,3alpha,5alpha,16beta,17beta)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)androstane-3,17-diol-17-acetate issubjected to salt formation with 3-bromopropene in a protic solvent under the action of a basic catalyst to obtain rocuronium bromide. The preparation method adopted in the invention is mild in reaction conditions, simple in post-treatment, and suitable for large-scale industrial application.
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Paragraph 0014; 0041-0042; 0044-0045; 0047-0048; 0050-0051
(2020/03/06)
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- Novel method for preparing rocuronium bromide
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The invention relates to a novel method for preparing rocuronium bromide 1-[17beta-acetoxyl-3alpha-hydroxyl-2beta-(4-morpholinyl)-androstane-16beta-yl]-1-(2-propenyl) pyrrole bromide, the problem of chemoselectivity of pyrrolidine open epoxy in an original line is solved, generation of byproducts is avoided, reaction yield is greatly improved, the production cost is reduced, column chromatography separation is avoided, and aftertreatment purification is implemented easily.
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- A new and efficient method for the synthesis of rocuronium bromide
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Rocuronium bromide has been used as an aminosteroid non-depolarizing neuromuscular blocker and muscle relaxant. In this work, a new and efficient route for preparing a key intermediate 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androstan-3α,17β-diol (6) was developed through a ring-opening of epoxide followed by introducing and pyrrolidine. Compound 6 can easily provide rocuronium bromide and the overall yield of compound 6 in 5 steps increased to 57.8%, which was higher than currently reported methods. Extraordinarily, this method would avoid the generation of disubstituted impurities E and F which are difficult to remove.
- Wu, Xue-Ying,Wang, Yao-Ling,Hai, Li,Gong, Ping,Wu, Yong
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p. 487 - 492
(2017/01/28)
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- Rocuronium bromide production technology
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The invention belongs to the field of chemical synthesis and particularly relates to a rocuronium bromide production technology. The technology includes the following steps that (2 beta, 3 alpha, 5 alpha, 16 beta, 17 beta)-2-(4-morpholinyl)-16-(1-pyrrolidyl)-5-androstane-3,17-glycol serves as an initial raw material, dichloromethane and 6N hydrochloric acid are added after acylation to generate (2 beta, 3 alpha, 5 alpha, 16 beta, 17 beta)-2-(4-morpholinyl)-16-(1-pyrrolidyl)-3-hydroxy-17-acetoxyl-5-androstane, finally, 3-bromopro is added, and a product is obtained through reaction. The whole technology is stable, easy to operate and mild in reaction condition, reagents and raw materials in use are little in toxin, treatment of three wastes is easy, the technology is suitable for industrial production, through analysis and research, product quality meets quality standards of clinical research, and stability is good.
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Paragraph 0031; 0032; 0033; 0034; 0035; 0036; 0037-0039
(2016/10/10)
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- NOVEL METHOD FOR SYNTHESIS OF NEUROMUSCULAR BLOCKING AGENTS
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The invention discloses a novel method for preparing neuromuscular blocking agents using aryl esters as a reagent of di-acylation as well as highly regioselective mono-acylation of androstane-diols.
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Page/Page column 12
(2016/03/13)
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- PROCESS FOR THE PREPARATION OF ROCURONIUM BROMIDE AND INTERMEDIATE THEREOF
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A novel regioselective process for preparing (2?, 3a, 5a, 16?, 17?)-17 acetoxy-3- hydroxy-2- (4-morpholinyl)- 16- (1-pyrrolidinyl) androstane, a known intermediate in the preparation of skeletal muscle relaxant rocuronium bromide in highly pure form.
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Page/Page column 9
(2009/03/07)
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- Processes for the synthesis of rocuronium bromide
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The invention encompasses processes for synthesizing 1-[17β-acetyloxy-3α-hydroxy-2β-(4-morpholinyl)-5α-androstan-16β-yl]-1-(2-propenyl)pyrrolidinium bromide (rocuronium bromide) and intermediates thereof.
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Page/Page column 15
(2008/06/13)
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- Method of reprocessing quaternary ammonium-containing neuromuscular blocking agents
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Provided is a method for reprocessing neuromuscular blocking agents containing a quaternary ammonium salt, e.g., Rocuronium bromide, using a novel dealkylation method. The process is effective in obtaining a highly pure product from a contaminated starting material by heating, optionally in the presence of an organic solvent, to produce a dealkyated product. The dealkylated product is purified, e.g., by crystallization, and converted by any known method to a stable, highly-pure neuromuscular blocking agent.
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Page/Page column 4
(2008/06/13)
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- Processes for the preparation of rocuronium bromide and intermediates thereof
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A novel process for preparing (2β,3α,5α,16β,17β)-17-acetoxy-3-hydroxy-2-(4-morpholinyl)-16-(1-pyrrolidinyl)androstane, a known intermediate in the synthesis of the skeletal muscle relaxant rocuronium bromide, is disclosed.
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Page/Page column 8
(2008/06/13)
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- Novel 2β-morpholino-androstane derivatives
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Compounds having the formula: STR1 wherein R 1 is H or an optionally substituted acyl group having 1-12 carbon atoms,R 2 is H or an acyl group having 1-12 carbon atoms andR 3 is C, N--CH 3 or a direct bond;and mono- or bisquaternary ammonium compounds thereof and acid addition salts of the non- or mono-quaternary ammonium compounds. Process for the preparation of these compounds. Compositions comprising at least one of the above compounds as the active ingredient. The compounds are favorable neuromuscular blocking agents.
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