公开(公告)号：US07071336B2

公开(公告)日：2006-07-04

申请号：US10892578

申请日：2004-07-16

申请人： Charles Auxilium Francis ,  Zhaiwei Lin ,  Christopher Arne Kaldahl ,  Kazimierz Grzegorz Antczak ,  Vijai Kumar

发明人： Charles Auxilium Francis ,  Zhaiwei Lin ,  Christopher Arne Kaldahl ,  Kazimierz Grzegorz Antczak ,  Vijai Kumar

IPC分类号： C07D471/00

CPC分类号： C07D489/08

摘要： Oxycodone is manufactured in high yields and with a high purity using a composition including a thebaine component into 14-hydroxycodeinone and then reduction of 14-hydroxycodeinone to oxycodone.

摘要翻译： 羟考酮以高产率制备，并且使用包含蒂巴因组分的组合物制成14-羟可待因酮，然后将14-羟可待因酮还原成羟考酮。

公开(公告)号：US06864370B1

公开(公告)日：2005-03-08

申请号：US10455202

申请日：2003-06-05

申请人： Zhaiwei Lin ,  Charles Auxilium Francis ,  Christopher Arne Kaldahl ,  Kazimierz Grzegorz Antczak ,  Vijai Kumar

发明人： Zhaiwei Lin ,  Charles Auxilium Francis ,  Christopher Arne Kaldahl ,  Kazimierz Grzegorz Antczak ,  Vijai Kumar

IPC分类号： A61K20060101 ,  C07D489/02 ,  C07D515/06 ,  C07D515/08

CPC分类号： C07D489/08

摘要： Oxycodone is manufactured in high yields and with a high purity using codeine or a salt of codeine as the starting material. The manufacturing process involves the following steps: (a) codeine or a codeine salt (e.g., codeine phosphate) is converted into the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine, (b) the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine resulting from step (a) is oxidized to yield the intermediate N-carboalkoxy- or N-carboaryloxynorcodeinone; (c) the intermediate N-carboalkoxy- or N-carboaryloxynorcodeinone resulting from step (b) is enolized with a base and the resultant enolate is thereafter methylated to yield the intermediate N-carboalkoxy- or N-carboaryloxynorthebaine; (d) the intermediate N-carboalkoxy- or N-carboaryloxynorthebaine resulting from step (c) is reduce to yield thebaine; (e) the thebaine resulting from step (d) is oxidized to yield the intermediate 14-hydroxycodeinone; and (f) the intermediate 14-hydroxycodeinone resulting from step (e) is hydrogenated to yield oxycodone.

摘要翻译： 以可待因或可待因盐为起始原料，以高产率和高纯度制造羟考酮。 制备方法包括以下步骤：（a）可待因或可待因盐（例如，磷酸可待因）被转化为中间体N-烷氧羰基或N-碳酰氧可卡因，（b）中间体N-烷氧羰基或N-碳酰氧可啡碱，得到 从步骤（a）中被氧化得到中间体N-烷氧羰基或N-碳酰氧可可醋酮;（c）步骤（b）得到的中间体N-烷氧羰基或N-碳酰氧可的可乐碱用碱碱化，然后将所得的烯醇化物 甲基化以产生中间体N-烷氧羰基或N-碳酰氧基异硫乙烯;（d）由步骤（c）得到的中间体N-烷氧羰基或N-碳酰氧基异硫乙烯被还原以产生蒂巴因;（e）由步骤（d） 被氧化得到中间体14-羟可待因酮; 和（f）将步骤（e）得到的中间体14-羟可待因酮氢化得到羟考酮。

公开(公告)号：US06790959B1

公开(公告)日：2004-09-14

申请号：US10455197

申请日：2003-06-05

申请人： Zhaiwei Lin ,  Charles Auxilium Francis ,  Christopher Arne Kaldahl ,  Kazimierz Grzegorz Antczak ,  Vijai Kumar

发明人： Zhaiwei Lin ,  Charles Auxilium Francis ,  Christopher Arne Kaldahl ,  Kazimierz Grzegorz Antczak ,  Vijai Kumar

IPC分类号： C07D47108

CPC分类号： C07D489/02 ,  C07D489/04

摘要： Thebaine is manufactured in high yields and with a high purity using codeine or a salt of codeine as the starting material. The manufacturing process involves the following steps: (a) codeine or a codeine salt (e.g., codeine phosphate) is converted into the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine; (b) the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine resulting from step (a) is oxidized to yield the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine; (c) the intermediate N-carboalkoxy- or N-carboaryloxynorcodeinone resulting from step (b) is enolized with a base and the resultant enolate is thereafter methylated to yield the intermediate N-carboalkoxy- or N-carboaryloxynorthebaine; and (d) the intermediate N-carboalkoxy- or N-carboaryloxynorthebaine resulting from step (c) is reduced to yield thebaine.

摘要翻译： 蒂巴因以可待因或可待因盐作为起始原料，以高产率和高纯度制造。 制造过程包括以下步骤：（a）可待因或可待因盐（例如磷酸可待因）被转化为中间体N-烷氧羰基或N-碳酰氧可卡因;（b）中间体N-烷氧羰基或N-碳酰氧可啡碱，得到 从步骤（a）中被氧化得到中间体N-烷氧羰基或N-碳酰氧可卡因;（c）步骤（b）得到的中间体N-烷氧羰基或N-碳酰氧可的可乐碱用碱碱化，然后将所得的烯醇化物 甲基化产生中间体N-烷氧羰基或N-碳酰氧基异硫乙烯; 和（d）由步骤（c）得到的中间体N-烷氧基 - 或N-碳酰氧基去硫敌
啶减少得到蒂巴因。