Electrochemical reactor and processes using the electrochemical reactor

Abstract

The present disclosure relates to an electrochemical reactor capable of processing an organic mixture comprising a suspension of a solid and a liquid, wherein the electrochemical reactor comprises an inner electrode, an outer electrode, wherein the inner electrode and the outer electrode are arranged concentrically forming a first cavity therebetween, a first inlet configured for introducing the liquid into the first cavity of the electrochemical reactor, a second inlet configured for introducing the solid into the first cavity of the electrochemical reactor, wherein the first inlet and the second inlet are arranged such that the liquid and the solid are introduced separately, wherein the inner electrode is configured to be rotatable around its longitudinal axis, wherein the inner electrode comprises one or more mixing elements. The present disclosure further relates to processes for the electrochemical N-demethylation and N- and O-demethylation, respectively, of an opioid precursor by means of the electrochemical reactor. The present disclosure further relates to a one-pot process for the N- and O-demethylation of an opioid precursor.

1 .- 10 . (canceled) 
     
     
         11 . An electrochemical reactor capable of processing an organic mixture comprising a suspension of a solid and a liquid, wherein the electrochemical reactor comprises:
 an inner electrode;   an outer electrode, wherein the inner electrode and the outer electrode are arranged concentrically forming a first cavity therebetween;   a first inlet configured for introducing the liquid into the first cavity of the electrochemical reactor;   a second inlet configured for introducing the solid into the first cavity of the electrochemical reactor, wherein the first inlet and the second inlet are arranged such that the liquid and the solid are introduced separately,   wherein the inner electrode is configured to be rotatable around its longitudinal axis,   wherein the inner electrode comprises one or more mixing elements.   
     
     
         12 . The electrochemical reactor according to  claim 11 ,
 wherein the electrochemical reactor further comprises a vessel enclosing the inner electrode and the outer electrode, wherein a second cavity is formed between the outer electrode and the vessel, wherein the second cavity is configured to be filled with a thermostated fluid.   
     
     
         13 . The electrochemical reactor according to  claim 11 ,
 wherein the inner electrode and/or the outer electrode comprise at least one of the group consisting of stainless steel, nickel, lead, bronze, platinum, tin, copper, titanium, chromium, zinc, magnesium aluminum, or any metal alloy thereof, or carbon materials, such as graphite, glassy carbon, boron doped diamond or composite materials made thereof.   
     
     
         14 . The electrochemical reactor according to  claim 11 , wherein the electrochemical reactor further comprises an outlet, such as an output valve, configured for allowing a removal of electrolyzed reaction mixture from the electrochemical reactor. 
     
     
         15 . The electrochemical reactor according to  claim 14 ,
 wherein the outlet is configured to be connected to an inlet of another reactor.   
     
     
         16 . The electrochemical reactor according to  claim 11 ,
 wherein a diameter of the inner electrode and a diameter of the outer electrode are selected such that a desired distance between the inner electrode and the outer electrode is achieved in accordance with the following formula:
   outer electrode diameter=inner electrode diameter+2×interelectrode gap
 
   
     
     
         17 . The electrochemical reactor according to  claim 11 ,
 wherein a distance between the inner electrode and the outer electrode is constant for a given process independent of a size of the electrochemical reactor.   
     
     
         18 . A process for preparing a compound of Formula (I) by means of an electrochemical reactor according to  claim 11 , the process comprising the steps of:
 providing a compound of Formula (II) in the electrochemical reactor,   providing a liquid containing an electrolyte and a solvent in the electrochemical reactor,   forming a suspension of the solid and the liquid by rotating the inner electrode having one or more mixing elements;   electrolyzing the suspension in the electrochemical reactor; and   subsequently treating the reaction mixture with an acid, wherein the acid is selected from the group consisting of hydrochloric acid, acetic acid and sulfuric acid;   wherein the compound of Formula (I) has the following structure:   
       
         
           
           
               
               
           
         
         wherein 
         each  -----  represents a single or double bond, provided that two double bonds are not adjacent to each other; 
         R 1  is selected from the group consisting of H, C 1-10  alkyl, C 6-10  aryl, C 3-10  cycloalkyl, C 1-10  alkylene-C 6-10  aryl, C 1-10  alkylene-C 3-10  cycloalkyl and a protecting group; 
         R 3  is selected from the group consisting of C 1-10  alkyl, C 6-10  aryl, C 3-10  cycloalkyl, C 1-10  alkylene-C 6-10  aryl, C 1-10  alkylene-C 3-10  cycloalkyl and a protecting group or is absent; 
         wherein one or more hydrogen atoms on the R 1  and R 3  groups may be replaced with F and/or Cl; 
         wherein the compound of Formula (II) has the following structure: 
       
       
         
           
           
               
               
           
         
         wherein 
         R 1 , R 3  and  -----  are as defined above; and 
         R 2  is selected from the group consisting of H, C(O)R 6 , S(O)R 6 , SO 2 R 6 , P(O)R 6 R 7 , P(O)(OR 6 )R 7 , and P(O)(OR 6 )(OR 7 ), and 
         R 6  and R 7  are each independently selected from the group consisting of C 3-10  cycloalkyl, C 3-10  heterocycloalkyl, C 3-10  cycloalkenyl, C 1-10  alkyl, C 2-10  alkenyl, C 6-10  aryl and C 5-10  heteroaryl, each of the groups being unsubstituted or substituted with one or more substituents independently selected from C 1-4  alkyl, O—C 1-4  alkyl, halogen, CN, NO 2 , C 6-10  aryl and O—C 6-10  aryl. 
       
     
     
         19 . The process according to  claim 18 ,
 wherein the step of providing a compound of Formula (II) in the electrochemical reactor comprises introducing the compound of Formula (II) in solid form into the electrochemical reactor via the second inlet; and   wherein the step of providing a liquid containing an electrolyte and a solvent in the electrochemical reactor comprises introducing the liquid into the electrochemical reactor via the first inlet.   
     
     
         20 . A process for preparing a compound of Formula (III) by means of an electrochemical reactor according to  claim 11 , the process comprising the steps of:
 providing a compound of Formula (II) in the electrochemical reactor,   providing a liquid containing an electrolyte and a solvent in the electrochemical reactor,   forming a suspension of the solid and the liquid by rotating the inner electrode having one or more mixing elements;   electrolyzing the suspension in the electrochemical reactor; and   subsequently treating the reaction mixture with hydrogen bromide (HBr);   wherein the compound of Formula (III) has the following structure:   
       
         
           
           
               
               
           
         
         wherein 
         each  -----  represents a single or double bond, provided that two double bonds are not adjacent to each other; 
         R 3  is selected from the group consisting of C 1-10  alkyl, C 6-10  aryl, C 3-10  cycloalkyl, C 1-10  alkylene-C 6-10  aryl, C 1-10  alkylene-C 3-10  cycloalkyl and a protecting group or is absent; 
         wherein one or more hydrogen atoms on the R 3  group may be replaced with F and/or Cl; 
         wherein the compound of Formula (II) has the following structure: 
       
       
         
           
           
               
               
           
         
         wherein 
         R 3  and  -----  are as defined above; and 
         R 1  is selected from the group consisting of H, C 1-10  alkyl, C 6-10  aryl, C 3-10  cycloalkyl, C 1-10  alkylene-C 6-10  aryl, C 1-10  alkylene-C 3-10  cycloalkyl and a protecting group, wherein one or more hydrogen atoms on the R 1  group may be replaced with F and/or Cl; 
         R 2  is selected from the group consisting of H, C(O)R 6 , S(O)R 6 , SO 2 R 6 , P(O)R 6 R 7 , P(O)(OR 6 )R 7 , and P(O)(OR 6 )(OR 7 ), and 
         R 6  and R 7  are each independently selected from the group consisting of C 3-10  cycloalkyl, C 3-10  heterocycloalkyl, C 3-10  cycloalkenyl, C 1-10  alkyl, C 2-10  alkenyl, C 6-10  aryl and C 5-10  heteroaryl, each of the groups being unsubstituted or substituted with one or more substituents independently selected from C 1-4  alkyl, O—C 1-4  alkyl, halogen, CN, NO 2 , C 6-10  aryl and O—C 6-10  aryl.