发明名称 | Method of synthesis of substituted hexitols such as dianhydrogalactitol | ||
摘要 | The present invention provides an efficient method of synthesizing and purifying dianhydrohexitols such as dianhydrogalactitol. In general, as applied to dianhydrogalactitol, the method comprises: (1) reacting dulcitol with a concentrated solution of hydrobromic acid at a temperature of about 80° C. to produce dibromogalactitol; (2) reacting the dibromogalactitol with potassium carbonate in t-butanol to produce dianhydrogalactitol; and (3) purifying the dianhydrogalactitol using a slurry of ethyl ether to produce purified dianhydrogalactitol. Another method produces dianhydrogalactitol from dulcitol; this method comprises: (1) reacting dulcitol with a reactant to convert the 1,6-hydroxy groups of dulcitol to an effective leaving group to generate an intermediate; and (2) reacting the intermediate with an inorganic weak base to produce dianhydrogalactitol through an intramolecular SN2 reaction. Other methods for the synthesis of dianhydrogalactitol from dulcitol are described. | ||
申请公布号 | US8921585(B2) | 申请公布日期 | 2014.12.30 |
申请号 | US201313933751 | 申请日期 | 2013.07.02 |
申请人 | Del Mar Pharmaceuticals | 发明人 | Brown Dennis M. |
分类号 | C07D303/14;C07D301/24;C07D301/26;C07D301/03;C07D301/02 | 主分类号 | C07D303/14 |
代理机构 | Ditthavong & Steiner, P.C. | 代理人 | Ditthavong & Steiner, P.C. |
主权项 | 1. A method for synthesizing dianhydrogalactitol (DAG) using dulcitol as a starting material comprising the steps of: (a) reacting dulcitol with hydrobromic acid (HBr), carbon tetrabromide (CBr4) and triphenylphosphine (Ph3P), para-toluenesulfonyl chloride (tosyl chloride), or trifluoromethanesulfonic anhydride (triflic anhydride) to convert the 1,6-hydroxy groups of dulcitol to 1,6-dibromo, 1,6-ditosylate, or 1,6-ditriflate groups, which provides 1,6-dibromodulcitol, 1,6-ditosyldulcitol or 1,6-ditriflatedulcitol; and (b) reacting the 1,6-dibromodulcitol, 1,6-ditosyldulcitol, or 1,6-ditriflatedulcitol with an inorganic weak base to produce DAG through an intramolecular SN2 reaction. | ||
地址 | Vancouver CA |