50288-62-5Relevant academic research and scientific papers
An Improved and Efficient Process for the Production of Highly Pure Dexmethylphenidate Hydrochloride
Xing, Long-Xuan,Shen, Cheng-Wu,Sun, Yuan-Yuan,Huang, Lei,Zheng, Yong-Yong,Li, Jian-Qi
, p. 1298 - 1303 (2017/03/27)
The present work describes an efficient and commercially viable process for the synthesis of dexmethylphenidate hydrochloride (1), a mild nervous system stimulant. The overall yield is 23% with ~99.9% purity (including seven chemical steps). Formation and control of possible impurities are also described in this report.
Dexmethylphenidate: An efficient process for the racemization of Unwanted (2 S,2 S or l - Threo)-α-Phenyl-α-(2-piperidyl)acetamide
Chavan, Anil B.,Gundecha, Sachin S.,Kadam, Pramod N.,Maikap, Golak C.,Gurjar, Mukund K.
experimental part, p. 1473 - 1475 (2011/09/20)
(2R,2 R)-d-threo-α-Phenyl-α-(2-piperidyl)acetamide (3), an advanced intermediate for dexmethylphenidate hydrochloride synthesis, is prepared by the resolution of dl-threo-α-phenyl-α-(2-piperidyl) acetamide (2) with dibenzoyl-d-tartaric acid in isopropanol with % yield and 99% ee. Although this process is efficient, there is a need to recycle the unwanted l-threo-amide and uncrystallized d-threo- amide from the mother liquor. The purpose of this study is 2-fold, first being the pollution issue to discard large amounts of unwanted isomer and the second to reduce the cost of (1). This aspect of recovery of unwanted isomer 4 formed the basic objective of this study. We have developed a new, simple, and cost-effective process for the racemization in which 4 was treated with potassium carbonate and N-chlorosuccinimide in DMF followed by treatment with DBU to afford the olefinic intermediate (5). Subsequent hydrogenation of the double bond provided dl-erythro-α-phenyl-α-(2-piperidyl)acetamide (6); the latter intermediate has already been converted into 1.
A PROCESS FOR THE PREPARATION OF ALPHA-ARYL-ALPHA-PIPERID-2-YL-ACETAMIDES AND THE ACID HYDROLYSIS THEREOF
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Page/Page column 4, (2008/06/13)
A process for the preparation of -aryl--piperid-2-yl-acetamides of formula (I) in which Ar is as defined in the disclosure, by catalytic reduction of α-aryl-α-pyridin-2-yl-acetamides (II) with rhodium catalysts. Acetamides of formula (II) can subsequently by hydrolysed to the corresponding arylacetic acids, e. g. ritalinic acid, a direct precursor of methylphenidate.
PROCESSES AND INTERMEDIATES FOR PREPARING 2-SUBSTITUTED PIPERIDINE STEREOISOMERS
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Page/Page column 5, (2008/06/13)
A process for preparing d-threo methyl ±- piperid-2-ylarylacetates of formula III: wherein R 1 is aryl having 6 to 28 carbon atoms, comprising the steps of: reacting a pyridine having formula I: wherein R 1 is aryl having 6 to 28 carbon atoms with hydrogen in an alkanoic acid having 1 to 10 carbon atoms and in the presence of a catalyst to provide a mixture of threo and erythro piperidine stereoisomers having formulas IIa-d: €?€?€? adding an alkyl alkanoate having 2 to 20 carbon atoms to said mixture, thereby precipitating alkanoate salts of said erythro stereoisomers preferentially with respect to alkanoate salts of said threo stereoisomers; reacting said erythro alkanoate salts with aqueous base to form said erythro stereoisomers; reacting said erythro stereoisomers with an acid resolving agent in an alkyl alcohol having 1 to 5 carbon atoms, thereby forming acid salts of said 1-erythro stereoisomers preferentially with respect to said d-erythro stereoisomers; reacting said 1-erythro acid salts with aqueous base to form said 1-erythro piperidine; reacting said 1-erythro piperidine with an alkali metal alkoxide having one to 10 carbon atoms in organic solvent, whereby forming said d-threo piperidine, and converting said d-threo piperidine to said d-threo methyl ±- piperid -2- ylarylacetate.
