A convenient method for synthesis of enantiomerically enriched methylphenidate from N-methoxycarbonylpiperidine.
[formula: see text] This report describes a new method to prepare optically active methylphenidate starting from piperidine. The method consists of a transformation of N-methoxycarbonylpiperidine to the corresponding alpha-methoxylated carbamate I by utilizing electrochemical oxidation followed by the coupling reaction with optically active Evans imides II to produce optically active methylphenidate derivatives III with high stereoselectivities, threo-(2R,2'R)-Methylphenidate (IV; Ar = Ph; Ritalin) was easily prepared from III in three steps.
Matsumura
Y
Y
Institute for Fundamental Research of Organic Chemistry, Kyushu University, Fukuoka, Japan. matumura@ms.ifoc.kyushu-u.ac.jp
Kanda
Y
Y
Shirai
K
K
Onomura
O
O
Maki
T
T
D018663:Adrenergic Agents / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D008774:Methylphenidate / Q000138:chemical synthesis*; D010880:Piperidines / Q000737:chemistry; D013237:Stereoisomerism
D018663:Adrenergic Agents; C410442:N-methoxycarbonylpiperidine; D010880:Piperidines; D008774:Methylphenidate