46727-91-7

Upstream product

• 3958-60-9 2-nitrophenylmethyl bromide 
• 27489-62-9 trans-4-hydroxycyclohexylamine 
• 4403-69-4 2-amino-1-benzylamine 
• 96039-76-8 trans-4-chloro-2-cyclohexen-1-yl acetate 

Relevant academic research and scientific papers

Ambroxol hydrochloride production process

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%.

Synthesis of chiral and achiral analogues of ambroxol via palladium-catalysed reactions

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.