One of the difficulties in the preparation of linezolid is the construction of the five-membered ring of oxazolone in its structure. The existing preparation process has the following problems:
(1) Using a high-boiling-point alcohol solvent process, the energy consumption required to evaporate this type of solvent is huge and the evaporation rate is slow, the prepared crystal form has agglomeration, and the appearance and purity are poor;
(2) The high-temperature suspension crystallization method in water is adopted. Since the solubility of linezolid in water varies greatly with temperature, the solubility is higher at high temperature and lower at low temperature, and a more stable crystal form will be precipitated during the cooling process. Crystal form I transforms into crystal form II relatively quickly at a low temperature, and the process for preparing linezolid crystal form I using this method is unstable, and the crystal form purity is not high.
In the field of linezolid, there is an urgent need for a method for preparing linezolid crystal form I with high purity and stable crystal form, which is easy to operate. Compared with the existing technical methods, the oxazolidinone antibiotic raw material medicine developed by Wuxi ZhangHua has the advantages of easy access to reagents, mild reaction conditions, environmental friendliness, and higher yield and purity.
Three-in-one process flow of flat plate filtration, washing and drying for oxazolidinone antibiotic raw materials
(1) Impurity removal of crude linezolid
In the three-in-one plate filter, washing and drying system, the crude linezolid is mixed with a specific solvent, filtered, and the filtrate is collected; after the crude linezolid is mixed with the solvent, stir at 85-105°C until the crude product dissolves, and then filter while hot , collect the filtrate.
(2) Crystallization of linezolid solvent after purification
Add the second solvent to the filtrate obtained in step (1), add the linezolid crystal form I seed, and carry out the crystallization process at 85-105°C; 2) Growing crystals at low temperature for 5-30 minutes, then slowly lowering the temperature to 0-10° C., and continuing to stir for 0.5-3 hours to precipitate crystals.
(3) Preparation of high-purity linezolid crystals
The precipitated crystals were separated in a three-in-one plate filtration, washing and drying process to obtain the crystalline form I of linezolid.
Starting from the simplification of the process, the three processes of filtration, washing and drying are completed on one machine, which reduces the number of process transfers; starting from the automation, cleanability and sterilization, it is improved to make the overall process more suitable for Production of sterile APIs.
The high-purity linezolid crystals prepared by three-in-one plate filtration, washing and drying for oxazolidinone antibiotic raw materials have compact crystal shape, good fluidity, low static electricity, and are easy to process. Wuxi ZhangHua three-in-one equipment solves the problems of the existing process The product has poor quality problems such as fluidity and static electricity, and has broad market application prospects.
The high-purity linezolid crystals prepared by three-in-one plate filtration, washing and drying for oxazolidinone antibiotic raw materials have compact crystal shape, good fluidity, low static electricity, and are easy to process. Wuxi ZhangHua three-in-one equipment solves the problems of the existing process The product has poor quality problems such as fluidity and static electricity, and has broad market application prospects.