The three-in-one filtration, washing and drying of zolidinone antibiotic raw materials

Linezolid is a type of zolidinone antibiotic. It was approved by the US FDA in 2000 for the treatment of bacteremia caused by vancomycin-resistant Enterococcus (VER), pneumonia and complex skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA), and bacteremia caused by penicillin-resistant Streptococcus pneumoniae (PRSP).

One of the difficulties in the preparation of linezolid is the construction of the oxazolidone five-membered ring in its structure. The existing preparation processes have the following problems:

(1) The process using high-boiling-point alcohol solvents requires huge energy consumption and a slow evaporation rate to discontinue such solvents. The prepared crystal forms have lumps, and both the appearance and purity are poor.

(2) The high-temperature suspension crystallization method in water is adopted. Due to the fact that the solubility of linezolid in water varies greatly with temperature, with a higher solubility at high temperatures and a lower solubility at low temperatures, more stable crystal forms will precipitate during the cooling process, resulting in the rapid transformation of crystal form I to crystal form II at lower temperatures. Therefore, the process for preparing crystal form I of linezolid using this method is unstable The purity of the crystal form is not high.

The field of linezolid urgently needs a simple and convenient method for preparing high-purity and crystal-stable linezolid crystal form I. Compared with the existing technical means, the three-in-one plate filtration, washing and drying of zolidinone antibiotic raw materials developed by Changzhou Baide has the advantages of easy availability of reagents, mild reaction conditions, environmental friendliness, higher yield and purity.

唑烷酮类抗生素原料药专用平板式过滤洗涤干燥三合一 工艺流程

  (1) 利奈唑胺粗品的去杂质
  在平板式过滤洗涤干燥三合一中，将利奈唑胺粗品与特定溶剂混合，过滤，收集滤液；利奈唑胺粗品与溶剂混合后，在85～105℃下搅拌直至粗品溶解，然后趁热过滤，收集滤液。
  (2) 纯化后利奈唑胺溶剂的结晶
  往步骤(1)得到的滤液中加入第二溶剂，加入利奈唑胺晶型I晶种，在85～105℃下进行结晶工艺；然后在回流温度(或在80～110℃或85～105℃下)下养晶5～30分钟，然后缓慢降温至0～10℃，继续搅拌0.5～3小时，从而析出晶体。
  (3) 制备高纯度利奈唑胺晶体
  在平板式过滤洗涤干燥三合一中，分离析出的晶体，得到利奈唑胺晶型I。从简化工序上入手，把过滤、洗涤、干燥三工序合在一机上完成，减少了工艺转序的次数；从自动化、可清洗与灭菌上入手，对其进行改进，使整体工艺更适宜于无菌原料药的生产。

The high-purity linazolid crystals prepared by the three-in-one plate filtration, washing and drying process for the raw materials of zolidinone antibiotics have a compact crystal shape, good fluidity, low static electricity and are easy to process. The three-in-one equipment of Wuxi Shuangrui has solved the quality problems of the existing process products in terms of poor fluidity and static electricity, and has a broad market application prospect.