Molecular Formula | C9H9Cl3O3S |
Molar Mass | 303.59 |
Density | 1.501±0.06 g/cm3(Predicted) |
Boling Point | 439.4±45.0 °C(Predicted) |
Use | Use S-2, 4-dichloro-a-(chloromethyl)-benzyl alcohol methanesulfonate Ester was used as luliconazole intermediate. |
invention patent
Application (patent) number:
CN201810230404.8
application date:
20180320
Public/Announcement Number:
CN108299156A
Public/announcement date:
20180720
applicant (patent):
AST (Chengdu) Biopharmaceutical Co., Ltd.
inventor:
Luo Jianye , Xu Xingbing , Guo Peng
National and provincial code:
CN510115
Abstract:
The invention discloses a new method for synthesizing a luliconazole key chiral intermediate, which belongs to the field of chemical synthesis. The invention is a key chiral intermediate (S) for the synthesis of luliconazole by preparing (R)2 halogenated 1(2,4 dichlorophenyl) ethanol, and then halogenated hydroxyl groups. 2,4 dichloro 1(1,2 dihaloethyl) benzene. This method in the preparation of chiral alcohol is completed in the aqueous phase, without the use of organic solvents, reducing the harm of organic solvents to the environment; The demand of chiral catalyst is less, and the catalyst can be recycled and reused under extraction conditions, greatly reducing the reaction cost; At the same time, using this method can make the final product (S)2,4 dichloro 1(1, the yield of 2 dihaloethyl) benzene is increased by industrial application.
CN 201210571630
application date:
Dec 25, 2012
Public/Announcement Number:
CN 103044192 A
applicant (patent):
Aist (Chengdu) Pharmaceutical Technology Co., Ltd.
inventor:
Liu Weiguo , Wang Canhui , Zhou Jia Yan Wu Liming
National and provincial code:
Sichuan; 51
Abstract:
The present invention belongs to the field of chemical synthesis process. In particular, it relates to the synthesis of luliconazole intermediate (S)-2, 4-dichloro-1-(1, 2-dichloroethyl) benzene. The technical problem to be solved by the present invention is that the existing synthesis method has high cost, low yield and is difficult to be industrialized. The technical scheme of the invention is to provide a synthesis method of luliconazole intermediate (S)-2, 4-dichloro-1-(1, 2-dichloroethyl) benzene, the method comprises the following steps: a, preparing a chiral catalyst; B, reacting a surfactant or a phase transfer catalyst with omega;-chloro-2, 4-dichloroacetophenone and a hydrogen source into the chiral catalyst; c, the reaction solution is extracted, recrystallized, and the solid is dried to obtain (R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol; d,(R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol reacts with oxalyl chloride, and the reaction solution is extracted, purified and dried to obtain product (S)-2, 4-dichloro-l-(1, 2-dichloroethyl) benzene. The present invention provides a new method for preparing (S)-2, 4-dichloro-1-(1, 2-dichloroethyl) benzene with high yield and low cost.
expand
sovereignty:
1. a method for the synthesis of luliconazole intermediate (S)-2, 4-dichloro-1-(1, 2-dichloroethyl) benzene, comprising the following steps, S)-N-(p-methylbenzenesulfonyl) -1, 2-diphenylethylenediamine and transition metal complex precursor preparation into chiral catalyst; B, the surfactant or phase transfer catalyst with & omega;-Chloro-2, 4-dichloroacetophenone and hydrogen source are added to the chiral catalyst in Step a for reaction; c. The reaction solution in Step B is extracted and recrystallized, and the solid is dried to obtain (R). -2-chloro-1-(2, 4-dichlorophenyl) ethanol; d, (R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol was subjected to chlorination reaction, and the reaction solution was extracted, purified and dried to obtain the product (S)-2, 4-dichloro-1-(1, 2-dichloroethyl) benzene.
invention patent
Application (patent) number:
CN201711498035.2
application date:
20171227
Public/Announcement Number:
CN108285909A
Public/announcement date:
20180717
applicant (patent):
Zhejiang Ocean University
inventor:
Tang Yunping , Zheng Jiawen , residual seedlings yandamu , Ding Guofang
National and provincial code:
CN330902
Abstract:
An enzymatic preparation method of luliconazole intermediate, which uses 2 chloro 1(2,4 dichlorophenyl) ethanone as a substrate, in the presence of a cofactor and a hydrogen donor, an asymmetric reduction reaction occurs to generate (S)2 chloro 1(2,4 dichlorophenyl) ethanol, comprising the following steps:(1) preparation of a ketoreductase: A single colony of recombinant E. Coli containing the ketoreductase gene was inoculated into liquid LB medium containing kanamycin resistance and cultured overnight at 37 °c; inoculate the culture obtained after activation into liquid LB medium containing kanamycin, shake culture at 37 ℃ to an OD of 0.60.8, and add IPTG at a final concentration of 0.1M, induced culture at 25 ℃ for 810H; Centrifuged to collect Thalli, and recombinant ketoreductase was obtained after ultrasonic wall breaking;(2)(S)2 chloro 1(2,4 dichlorophenyl) preparation of ethanol: the substrate 2 chloro 1(2,4 dichlorophenyl) ethanone is added to the buffer and a certain amount of cofactor NAD(P) and isopropanol, the biocatalytic reaction was carried out by adding recombinant ketoreductase at 30 ℃. After the reaction was finished, ethyl acetate was added for extraction to obtain the product (S)2 chloro 1(2,4 dichlorophenyl) ethanol.
Uses | S-2, 4-dichloro-A-( chloromethyl)-benzyl alcohol mesylate is used as luliconazole intermediate. |