On July 30, 2012, Zhang, Wei; Chen, Niangen; Huang, Jian; Zhai, Ruirui; Fu, Naiguang published an article.Application of 39512-49-7 The title of the article was Study on synthetic and salifying process of loperamide hydrochloride. And the article contained the following:
To study the preparation of the synthetic process of loperamide hydrochloride, a drug which was widely used in the treatment of acute diarrhea with low side effect. Loperamide hydrochloride was synthesized from 2, 2-diphenyl-4-hydroxybutyric acid-γ-lactone as raw material via ring-opening, SN2 substitution, acidylation, quaternization, condensation and salifying. In the first step, when the reaction time was 24 h and temperature was 25°C, the yield was 81%. In the second step, when the molar ratio of n(SOCl2):n(2,2-phenyl-4-bromobutyric acid)=2:1 and temperature was reflux, the content of 4-bromo-2, 2-diphenylbutyroyl chloride(4) was 97.25%. And the key intermediate dimethyl(tetrahydro-3, 3-diphenyl-2-furylidene)ammonium bromide(5) was obtained with the yield increased from 50%(literature reported) to 68% when the molar ratio of n(4):n(Na2CO3):dimethylamine=1.0:1.2:1.5 and temperature was 0∼5°C. When the molar ratio of n(5):n(4-p-chlorophenyl-4-piperidinol):n(Na2CO3)=1.0:1.2:1.1, loperamide(6) was obtained with yield of 85%. After simple salification, the target compound 1 was synthesized from(6) with the yield of 89.6%. The overall yield was 34% and its structure was characterized by IR, 1H-NMR, 13C-NMR and MS spectra. Some drawbacks in the literature was improved and the method was easy for synthesis and suitable for industrial manufacturing The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Application of 39512-49-7
The Article related to loperamide hydrochloride synthetic salifying process, Pharmacology: Methods and other aspects.Application of 39512-49-7
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem