# US 7,465,830 B2 · Method of preparing pseudonorephedrine > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,465,830 B2 - Document ID: US7465830B2 - Status: Granted - Kind: B2 - Application number: 11/836,510 - Filed: 2007-08-09 - Published: 2008-03-06 - Granted: 2008-12-16 - Earliest claimed: 2006-08-29 - Assignees: Illinois State University - Inventors: Shawn R. Hitchcock; Jonathan Andrew Groeper - Web page: https://patentgrep.com/patent/US7465830B2 ## CPC - C07C 215/30: containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton - C07C 213/00: Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton - C07B 2200/07: Optical isomers - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F) ## Abstract A method of making high diastereoselective and enantiomerically pure pseudonorephedrine and the hitherto unknown compound (1R,2R) pseudonorephedrine. ## Claims ### Claim 1 A method of making (1S,2S) pseudonorephedrine comprising: A) providing (1R,2S) norephedrine as a starting material; B) acylating the amine to produce as a secondary carbamate derivative; C) treating the secondary carbamate derivative to displace the alcohol and invert the phenyl group to produce the oxazolidinones as a major product, and as a minor product; and D) hydrolyzing the major product oxazolidinone to form (1S,2S) pseudonorephedrine. ### Claim 2 (depends on 1) The method of claim 1 in which the acylation is achieved by treating the norephedrine with di-tert-butyl dicarbonate and triethylamine. ### Claim 3 (depends on 1) The method of claim 1 in which the oxazolidinones are produced by treating the secondary carbamate derivative with triethylamine and methanesulfonyl chloride to displace the alcohol and invert the phenyl group. ### Claim 4 (depends on 3) The method of claim 3 in which the solution is refluxed in dichloromethane or tetrahydrofuran at a reflux temperature of about 45-50° C. ### Claim 5 (depends on 1) The method of claim 1 in which the major product oxazolidinone is purified by triturating in a polar organic solvent or by exposing the major product oxazolidinone polar solvent to a non-polar solvent to recrystalize the product. ### Claim 6 (depends on 1) The method of claim 1 in which the hydrolysis is carried out using a base strong enough to open the major product oxazolidinone in which the metal of the base does not adversely interact with the end product. ### Claim 7 (depends on 6) The method of claim 6 in which the base is chosen from the group consisting of LiOH, NaOH, KOH, Ca(OH)2, and Mg(OH)2. ### Claim 8 (depends on 1) The method of claim 1 in which the major product oxazolidinone is hydrolyzed in a LiOH/H2O solution. ### Claim 9 (depends on 1) The method of claim 1 in which the hydrolysis is carried out at a temperature of about 80-100° C. ### Claim 10 (depends on 1) The method of claim 1 carried out as a one pot process in an organic solvent without stopping at the end of each reaction, extracting intermediate products, purifying and continuing with the next reaction. ### Claim 11 (depends on 10) The method of claim 10 in which any organic solvent is removed before the hydrolysis step while the solution is maintained at a temperature of about 60° C. and then the mixture is heated to a temperature of about 80-100° C. ### Claim 12 A method of making (1R,2R) pseudonorephedrine comprising: A) providing (1S,2R) norephedrine as a starting material; B) acylating the amine to produce as a secondary carbamate derivative; C) treating the secondary carbamate derivative to displace the alcohol and invert the phenyl group to produce the oxazolidinones as a major product; and as a minor product; and D) hydrolyzing the major product oxazolidinone to form (1R,2R) pseudonorephedrine. ### Claim 13 (depends on 12) The method of claim 12 in which the acylation is achieved by treating the norephedrine with di-tert-butyl dicarbonate and triethylamine. ### Claim 14 (depends on 12) The method of claim 12 in which the oxazolidinones are produced by treating the secondary carbamate derivative with triethylamine and methanesulfonyl chloride to displace the alcohol and invert the phenyl group. ### Claim 15 (depends on 14) The method of claim 14 in which the solution is refluxed in dichloromethane or tetrahydrofuran at a reflux temperature of about 45-50° C. ### Claim 16 (depends on 12) The method of claim 12 in which the major product oxazolidinone is purified by triturating in a polar organic solvent or by exposing the major product oxazolidinone polar solvent to a non-polar solvent to recrystalize the product. ### Claim 17 (depends on 12) The method of claim 12 in which the hydrolysis is carried out using a base strong enough to open the major product oxazolidinone in which the metal of the base does not adversely interact with the end product. ### Claim 18 (depends on 17) The method of claim 17 in which the base is chosen from the group consisting of LiOH, NaOH, KOH, Ca(OH)2, and Mg(OH)2. ### Claim 19 (depends on 12) The method of claim 12 in which the major product oxazolidinone is hydrolyzed in a LiOH/H2O solution. ### Claim 20 (depends on 12) The method of claim 12 in which the hydrolysis is carried out at a temperature of about 80-100° C. ### Claim 21 (depends on 12) The method of claim 12 carried out as a one pot process in an organic solvent without stopping at the end of each reaction, extracting intermediate products, purifying and continuing with the next reaction. ### Claim 22 (depends on 21) The method of claim 21 in which any organic solvent is removed before the hydrolysis step while the solution is maintained at a temperature of about 60° C. and then the mixture is heated to a temperature of about 80-100° C.