D(-)-α-(4-乙基-2,3-双氧代哌嗪-1-甲酰胺基)对羟基苯乙酸的合成

用双 三氯甲基碳酸酯(三光气)代替光气和4 乙基 2,3 双氧代哌嗪发生酰氯化反应,制备氧哌嗪酰氯(EOCP),进而和D(-) α 对羟基苯甘氨酸(p HPG)缩合,水解合成了D(-) α (4 乙基 2,3 双氧代哌嗪 1 甲酰胺基)对羟基苯乙酸(OH—EPCP)。酰氯化反应条件为:-15℃,n(Nu)∶n(三光气)∶n(氧哌嗪)=0 08∶0 4∶1 0,反应4h。EOCP收率大于90%。缩合反应温度15～20℃,n(EOCP)∶n(p HPG)=1 1∶1 0,反应3h。然后在室温下水解,得到白色粉末状产品。经精制后,w(OH—EPCP)>98 0%,收率(相对于p HPG用量)达88 0%。用元素分析、IR、1HNMR和MS对产品进行表征,证明了合成方法的可靠性。

Preparation of D(-)-α-(4-Ethyl-2,3-dioxopiperazine-1-carboxamido)-p-hydroxyphenylacetic Acid

4 Ethyl 1 chloroformyl 2,3 dioxopiperazine(EOCP) was prepared from 4 ethyl 2,3 dioxopiperazine by reaction of bis(trichloromethyl) carbonate(triphosgene) instead of phosgene.It is necessary to add a nucleophile Nu as initiator to triphosgene solution.The chloroformylation reaction was conducted at -15 ℃ for 4 h with n(Nu)∶n(triphosgene)∶n(4 ethyl 2,3 dioxopiperazine)=008∶04∶10.The yield of EOCP was>90%.Then D(-) α (4 ethyl 2,3 dioxopiperazine 1 carboxamido) p hydroxyphenylacetic acid (Hydroxyl EPCP) was prepared by condensation of D(-) α p hydroxyphenylglycine(p HPG) with EOCP at 15-20 ℃ for 3 h with n(EOCP)∶n(p HPG)=11∶10.After hydrolysis at room temperature,white powdered product was obtained in 880% yield (based on p HPG) with product purity w(Hydroxyl EPCP) >98%.The product was characterized by elementary analysis,IR,1HNMR and MS.The results showed the reliability of this new synthetic method.