18683-91-5Relevant articles and documents
Preparation method of ambroxol hydrochloride
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, (2021/06/23)
The invention discloses a preparation method of ambroxol hydrochloride, which comprises the steps of 1) reacting (A) o-aminodibromobenzaldehyde (I) with (E)-p-aminocyclohexanol (II) to obtain Schiff base; 2) reducing a carbon-nitrogen double bond C = N by (E)-4-[(2-amino-3, 5-dibromobenzylidene) amino] cyclohexanol to obtain ambroxol; and 3) salifying to obtain the finished product ambroxol hydrochloride (compound 1). The route is simple, the product is obtained through condensation, reduction and salification, aldehyde and amido react to generate Schiff base, and the reaction yield is relatively high; and in the reduction reaction of ambroxol, a sodium borohydride zinc chloride complexing system is adopted, the catalytic effect is better, and the production cost is further reduced. The method has the advantages of simple process, low safety and environmental protection risk, easily available raw materials, simple equipment requirements, very little generated wastewater, and easy treatment of three wastes to reach the standard.
Ambroxol hydrochloride synthesis method
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Paragraph 0016; 0024; 0027-0028; 0031; 0034-0035; 0038; 0041, (2018/04/01)
The invention discloses an ambroxol hydrochloride synthesis method, which comprises: in a first-step bromination reaction, adding water to o-methylaniline, cooling, adding a hydrobromic acid solutionin a dropwise manner, carrying out a reaction, controlling the temperature at 30-60 DEG C, adding bromine, hydrogen peroxide and a sodium hydroxide solution in a dropwise manner, carrying out a reaction, and filtering to obtain 2,4-dibromo-6-(bromomethyl)aniline; and in a second-step amination reaction, sequentially adding DMF, potassium carbonate and trans cyclohexanolamine to the prepared 2,4-dibromo-6-(bromomethyl)aniline, heating to a temperature of 90-110 DEG C, carrying out thermal insulation for 2-6 h, adding toluene, carrying out stirring crystallization, and filtering to obtain ambroxol. The invention provides a new ambroxol hydrochloride synthesis process, wherein the reaction conditions are artfully controlled at the benzene ring section, the halogens at the ring and the side chain are respectively replaced with bromine for replacing chlorine, and the bromination is sequentially performed and is completed in one step, such that the selectivity of the linking reaction betweenthe benzene ring and the cyclohexyl ring is good, and the yield is high.
Synthesis, structural characterization and Hirshfeld analysis studies of three novel co-crystals of trans-4-[(2-amino-3,5-dibrobenzyl) amino] cyclohexanol with hydroxyl benzoic acids
Ma, Yu-Heng,Lou, Ming,Sun, Qing-Yang,Ge, Shu-Wang,Sun, Bai-Wang
, p. 111 - 120 (2015/02/05)
Combination of active pharmaceutical ingredients, trans-4-[(2-amino-3,5-dibrobenzyl) amino] cyclohexanol (AMB) and some organic acids, e.g., p-hydroxybenzoic acid (PHBA), m-hydroxybenzoic acid (MHBA), and 3,4-dihydroxy benzoic acid (DHBA), yield three novel co-crystals characterized by X-ray single-crystal, Fluorescence spectroscopy and thermal analysis (DSC and TGA), which included co-crystal 1 with 2:2: 1 stoichiometry of AMB, PHBA and H2O, co-crystal 2 with 1:1 stoichiometry of AMB and MHBA, and co-crystal 3 with 1:1:1 stoichiometry of AMB, DHBA and CH3OH. Constituents of the co-crystalline phase were also investigated in terms of Hirshfeld surfaces. In the crystal lattice, a three-dimensional hydrogen-bonded network is observed, including formation of a two-dimensional molecular scaffolding motif. Hirshfeld surfaces and fingerprint plots of three co-crystals show that structures are stabilized by H?H, N-H?O, H?Br and C?H intermolecular interactions. Besides, the studies of the solubility showed that this co-crystal strategy could promote the solubility of AMB and follow the order: co-crystal 1 co-crystal 2 co-crystal 3.