公开(公告)号：US20090234139A1

公开(公告)日：2009-09-17

申请号：US11992212

申请日：2006-09-19

申请人： Lovro Selic ,  Gregor Vilfan ,  Uros Urleb

发明人： Lovro Selic ,  Gregor Vilfan ,  Uros Urleb

IPC分类号： C07D205/04

CPC分类号： C07F7/1892 ,  Y02P20/55

摘要： A novel process for the preparation of 1′-hydroxy-2′-substituted cyclohexyl azetidin-2-one compound of formula 2, which is important intermediate in the synthesis of trinems, is described by epoxide ring opening of (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(1′R,2′S,3′R)-1′,2′-epoxycyclohexan-3′-yl]azetidin-2-one of formula 1 with the nucleophile compound of formula RYH, where nucleophile may act as solvent itself if the nucleophile is in the liquid form, in a suitable solvent and in the presence of a suitable catalyst from the group of salt of trifluoromethane sulfonic acid, preferably ytterbium (III) trifluoromethanesulfonate, stannous (II) trifluoromethanesulfonate or dysprosium (III) trifluoromethanesulfonate, under a) ultrasonic irradiation or b) under microwave irradiation of the reaction mixture following by isolation and purification of the desired compound. A variant of the novel process describes ring epoxide opening of the starting compound of formula 1 with the compound of formula NH4X in a suitable solvent under a) microwave irradiation or b) without microwave irradiation to obtain the desired compound of formula 2. Instead of compound of formula 1 a compound of formula 6 may be used as starting compound where any other suitable hydroxy protecting group known in the art may be used in the formula of the starting compound.

摘要翻译： （3S，4R） - 环糊精的环氧化物开环描述了制备式（2）的1'-羟基-2'-取代的环己基氮杂环丁烷-2-酮化合物的新方法，其是三聚氰胺合成中的重要中间体。 3 - [（1R）-1-（叔丁基二甲基甲硅烷氧基）乙基] -4 - [（1'R，2'S，3'R）-1'，2'-环氧环己烷-3'-基]氮杂环丁-2-酮 式1与式RYH的亲核化合物反应，其中如果亲核试剂为液体形式，亲核试剂可以在合适的溶剂中和在三氟甲烷磺酸盐的合适的催化剂存在下，作为溶剂本身，优选 （a）三氟甲磺酸镱（II），三氟甲磺酸亚锡（II），三氟甲磺酸镝（III），或b）在微波照射反应混合物之后，分离和纯化所需化合物。 新方法的变体描述了式Ⅰ的起始化合物与式NH 4 X的化合物在合适的溶剂中在a）微波照射下或b）没有微波照射得到所需的式2化合物的环氧化物开环。代替化合物 式1的化合物可以用作起始化合物，其中本领域已知的任何其它合适的羟基保护基可以用于起始化合物的式中。