107814-37-9

Basic information

• Product Name: AMbroxol EP IMpurity D
• Synonyms: AMbroxol EP IMpurity D;cis-4-[[(2-AMino-3,5-dibroMophenyl)Methyl]aMino]cyclohexanol;rac-cis-AMbroxol;AMbroxol IMpurity D;Cyclohexanol,4-[[(2-amino-3,5-dibromophenyl)methyl]amino]-,cis-;Ambroxol impurity D HCl;cis-4-((2-Amino-3,5-dibromobenzyl)amino)cyclohexanol
• CAS NO: 107814-37-9
• Molecular Formula: C₁₃H₁₈Br₂N₂O
• Molecular Weight: 378.10282
• EINECS: 200-158-5
• Mol File: 107814-37-9.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 468.6±45.0 °C(Predicted)
• Appearance: /
• Density: 1.70±0.1 g/cm3(Predicted)
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 15.12±0.40(Predicted)
• CAS DataBase Reference: AMbroxol EP IMpurity D(CAS DataBase Reference)
• NIST Chemistry Reference: AMbroxol EP IMpurity D(107814-37-9)
• EPA Substance Registry System: AMbroxol EP IMpurity D(107814-37-9)

Safety Data

• Hazardous Substances Data: 107814-37-9(Hazardous Substances Data)

Usage

Uses

cis-Ambroxol is the cis-isomeric impurity of Ambroxol (A575905). cis-Ambroxol is a metabolite Bromhexine (B678600).

Upstream product

• 27489-62-9 trans-4-hydroxycyclohexylamine 
• 50739-76-9 (2-amino-3,5-dibromophenyl)methanol 
• 50910-55-9 3,5-dibromo-2-amino benzaldehyde 
• 96039-76-8 trans-4-chloro-2-cyclohexen-1-yl acetate 
• 82736-39-8 cis-1-acetoxy-4-chlorocyclohex-2-ene 
• 95-53-4 o-toluidine 
• 552-89-6 2-nitro-benzaldehyde 
• 861787-48-6 3,5-dibromo-2-nitro-benzaldehyde 
• 23828-92-4 ambroxol hydrochloride 

Downstream Products

• 1241045-90-8 (2R,3R,4S,5S,6S)-2-(4-(2-amino-3,5-dibromobenzylamino)-cyclohexyloxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 
• 1445719-53-8 4-(2-amino-3,5-dibromobenzylamino)cyclohexanone 
• 23828-92-4 ambroxol hydrochloride 
• 96989-76-3 1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purine-7-acetic acid trans-4-[[(2-amino-3,5-dibromophenyl)methyl]amino]cyclohexanol 
• 301669-90-9 4-[(2-tert-butoxycarbonylamino-3,5-dibromophenyl)methylamino]trans cyclohexanol 

Relevant articles and documents

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.

Preparation method of ambroxol hydrochloride

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

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.