手性(2R,3R)-2,3-环氧丁酸盐的制备

Preparation of chiral (2R,3R)-2,3-epoxybutanoate salt

目的用L-苏氨酸制备手性(2R,3R)-2,3-环氧丁酸盐,并对成盐方法、晶型、稳定性进行研究。方法 L-苏氨酸经重氮化、环氧化形成手性(2R,3R)-2,3-环氧丁酸,再与无机或有机碱成盐。研究酸碱度、温度、溶剂、溶液体系等对成盐的影响,XRD、SEM考察盐的晶型和形貌。测试盐与胺的反应,并监测其稳定性。结果得到手性(2R,3R)-2,3-环氧丁酸锂、钠、钾、钙、镁、铵、一甲胺、二甲胺、对甲氧基苯胺盐,IR、1H-NMR、MS确证结构,1年内稳定。液-液或气-液成盐较好,低温下在醇、酮溶剂中钠、钾盐收率超过80%。XRD、SEM显示,溶媒法环氧丁酸盐为晶态,冻干环氧丁酸钠盐为无定形态,粒径小于10μm。环氧丁酸盐与胺反应手性保持,冻干粉反应活性较高。结论环氧丁酸盐稳定,制备工艺简单,质量可控,可用于碳青霉烯类抗生素的制备。

Objective The Chiral （2R,3R）-2,3-epoxybutanoate salt was prepared from L-threonine, their producing method, crystal form and stability were investigated. Methods Chiral （2R,3R）-2, 3,epoxy butyrate was derived from L-threonine under diazotization and cyclization reaction, further, it reacts with inorganic or organic base to achieve the relative salt. The influence of solvent system, acidity, temperature to salt were studied. Moreover, the crystal form and their reactivity were investigated. XRD, SEM were used to inspect salt crystal and morphology. Tested and verified the reactivity of salt with amine and monitored their stability. Result Obtain chiral lithium, sodium, potassium, calcium, magnesium, ammonium, monomethylamine, 4-methoxyaniline （2R,3R）-2,3- epoxybutanoate, their structures were identified by IR,1H-NMR, MS, the stability continued over a year, better solvent system is using liquid-liquid or gas-liquid, potassium and sodium salt yield is more than 80% in alcohol or ketone solvent at low temperature. XRD, SEM test showed that （2R,3R）-2, 3-epoxybutanoate salt has different crystal form for each other, freeze-dried sodium salt powder is amorphous, particle size less than 10μm. their chirality maintain good after reacting with amine, reactivity of freeze-dried powder is better than that of crystal powder. Conclusion All kinds of epoxybutanoate salt are stable, the manufacture process is simple, under quality control, and it can be used for preparation of carbapenem antibiotics.