- Ambroxol hydrochloride production process
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The invention relates to an ambroxol hydrochloride production process which comprises the following steps: dropwise adding o-nitrobenzyl bromide into trans-4-aminocyclohexanol to carry out condensation reaction to obtain an N-(o-nitrophenyl)-trans-4-aminocyclohexanol chloroform reaction solution, adding hydrochloric acid, and separating the solution to obtain an N-(o-nitrophenyl)-trans-4-aminocyclohexanol hydrochloride aqueous solution; adding toluene into a hydrochloride aqueous solution to obtain an N-(o-aminophenyl)-trans-4-aminocyclohexanol toluene reaction solution; adding sulfuric acid into the toluene reaction solution to obtain an N-(o-aminophenyl)-trans-4-aminocyclohexanol sulfuric acid reaction solution; and carrying out bromination reaction in a sulfuric acid reaction solution, filtering out 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl)benzylamine salt, and dissolving, purifying and refining the benzylamine salt to obtain ambroxol hydrochloride. According to the preparation method, o-nitrobenzyl bromide is adopted as a starting raw material and is subjected to condensation with trans-4-aminocyclohexanol, reduction, bromination and salification refining, the ambroxol hydrochloride is obtained, the total yield reaches 85% or above, the raw materials are easy to obtain, operation is convenient and fast, and the raw material cost can be saved by 40%-50%.
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Paragraph 0034-0037
(2021/09/29)
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- Synthesis of chiral and achiral analogues of ambroxol via palladium-catalysed reactions
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Chiral cis- and trans-4-aminocyclohex-2-enols and achiral 4-aminocyclohexanols, which all are analogues of ambroxol, are prepared via stereoselective allylic substitution of cyclohex-2-ene-1,4-diol derivatives or 1-acetoxy-4-chlorocyclohex-2-ene. The chiral target molecules are obtained in enantiomerically pure form by employing a previously described enantiodivergent synthesis of cis- and trans-4-aminocyclohex-2-enols. It has been found that bis(amine) nucleophiles 7a and 7b react only at the benzylic amino group under the conditions employed.
- Larsson, Anna L. E.,Gatti, Roberto G. P.,Baeckvall, Jan-E.
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p. 2873 - 2877
(2007/10/03)
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