- Preparation method of ambroxol hydrochloride
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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.
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- Synthetic method of ambroxol hydrochloride
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The invention relates to a synthetic method of ambroxol hydrochloride. The method comprises the following steps: reacting isatoic anhydride serving as an initial raw material with trans-4-aminocyclohexanol to obtain trans-4-[(2-aminobenzoyl) amino] cyclohexanol; carrying out bromine substitution on the trans-4-[(2-aminobenzoyl) amino] cyclohexanol to obtain trans-4-[(2-amino-3, 5-dibromo benzoyl)amino] cyclohexanol; trans-4-[(2-amino-3, 5-dibromobenzoyl) amino] cyclohexanol is subjected to amido bond reduction, so that ambroxol is obtained; and finally salifying the ambroxol to obtain the ambroxol hydrochloride. The method is easy to operate, mild in condition, high in yield, environmentally friendly, stable in raw material property, easy to store and suitable for industrial mass production.
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Paragraph 0083-0094
(2021/02/10)
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- Trans-Selective and Switchable Arene Hydrogenation of Phenol Derivatives
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A trans-selective arene hydrogenation of abundant phenol derivatives catalyzed by a commercially available heterogeneous palladium catalyst is reported. The described method tolerates a variety of functional groups and provides access to a broad scope of trans-configurated cyclohexanols as potential building blocks for life sciences and beyond in a one-step procedure. The transformation is strategically important because arene hydrogenation preferentially delivers the opposite cis-isomers. The diastereoselectivity of the phenol hydrogenation can be switched to the cis-isomers by employing rhodium-based catalysts. Moreover, a protocol for the chemoselective hydrogenation of phenols to cyclohexanones was developed.
- Bergander, Klaus,Glorius, Frank,Heusler, Arne,Wollenburg, Marco
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p. 11365 - 11370
(2020/11/24)
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- Preparation method of ambroxol hydrochloride
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The invention relates to a preparation method of ambroxol hydrochloride, and the method comprises the following steps: carrying out aldehyde group protection on o-nitrobenzaldehyde, and reducing hydrazine hydrate in the presence of a catalyst NiCoB/TiO2 to obtain a compound 3; carrying out bromination reaction on the compound 3 under the action of molecular bromine and hydrogen peroxide, and carrying out deprotection to generate a compound 2; and carrying out aldehyde reductive amination reaction with trans-4-aminocyclohexanol under the action of catalysts NaBH (OAc) 3 and LiClO4, and salifying to obtain the ambroxol hydrochloride. The method has the advantages of mild conditions, simple steps, environmental friendliness, easily stored raw materials and high yield, and is suitable for industrial production.
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- Method for preparing ambroxol hydrochloride
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The invention discloses a method for preparing ambroxol hydrochloride. The method comprises the steps of (1) using o-aminodibromobenzaldehyde and trans-p-aminocyclohexanol as raw materials, using 4-dimethylaminopyridine as a catalyst, carrying out a condensation reaction in a reaction solvent, and after the reaction, obtaining a compound (I) by post-treatment; (2), using formic acid or formate which is cheap and easily availableas a reducing agent, using palladium carbon, palladium chloride, raney nickel or platinum carbonas a catalyst, making the compound (I) be subjected to a reduction reaction in a reaction solvent, and after the completion of the reaction, obtaining a compound (II) by post-treatment; (3), making the compound (II) be reacted with hydrochloric acid in a reaction solvent,and after the completion of the reaction,obtaining a compound (III) by post-treatment.The method adopts o-aminodibromobenzaldehyde and trans-p-aminocyclohexanol as raw materials, uses condensation and reduction of the formic acid or formate, and forms salt from hydrochloric acid to obtain the ambroxol hydrochloride. Themethod is safe and environmentally friendly, has small pollution, good economic benefit and simple operation and is suitable for industrial production.
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Paragraph 0044-0083
(2019/07/16)
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- Ambroxol hydrochloride compound containing one-tenth water and pharmaceutical composition thereof
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The invention discloses an ambroxol hydrochloride compound containing one-tenth water and a pharmaceutical composition thereof. Each mole of ambroxol hydrochloride comprises one-tenth mole of water. An infrared spectrum of the ambroxol hydrochloride compound has characteristic absorption peaks at the positions with the wave numbers of 3398.7+/-2cm, 3286.5+/-2cm, 3198.1+/-2cm, 2943.4+/-2cm, 2765.8+/-2cm, 2713.7+/-2cm, 1631.4+/-2cm, 1584.1+/-2cm, 1459.0+/-2cm, 1066.0+/-2cm and 866.5+/-2cm. The ambroxol hydrochloride compound containing one-tenth waterhas low hygroscopicity and impurity content, high thermodynamic stability and a wider application prospect.
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Paragraph 0038; 0040-0044; 0046-0050; 0052-0055
(2019/01/23)
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- Ambroxol hydrochloride synthesis method
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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.
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Paragraph 0019; 0024; 0029-0031; 0036-0038; 0043-0045; 0050
(2018/04/01)
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- Ambroxol hydrochloride synthetic method
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The invention belongs to the field of pharmaceutical synthesis and particularly discloses a synthesis method of ambroxol hydrochloride. The synthesis method comprises the steps of brominating o-nitrobenzaldehyde serving as a starting raw material to obtain 2-nitro-3, 5-dibromobenzaldehyde; reacting the obtained 2-nitro-3, 5-dibromobenzaldehyde and trans-4-aminocyclohexanol; and then, reducing and salifying hydrochloride to finally prepare ambroxol hydrochloride. The synthesis method disclosed by the invention is low in raw material cost, simple in operation, safe and environment-friendly, capable of simplifying the production process and increasing the yield and purity of products and suitable for industrial production.
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- Pharmaceutical compositions containing an effervescent acid-base couple
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A pharmaceutical composition in the form of effervescent tablets comprising an active ingredient and an effervescent blend, comprising an acidic component and sodium glycine carbonate as alkaline components. Preferred acid components are fumaric acid, maleic acid, and their salts. Tablets are prepared in normal thermohygrometric conditions and with standard tabletting equipment. A pre-granulation process is also disclosed.
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- Pharmaceutical compositions containing an effervescent acid-base couple
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A pharmaceutical composition in the form of effervescent tablets comprising an active ingredient and an effervescent blend, wherein the effervescent blend comprises an acidic component and sodium glycine carbonate as alkaline components. Preferred acid components are fumaric acid, maleic acid, and their salts. Tablets are prepared in normal thermo-hygrometric conditions and with standard tabletting equipment.
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