ERIC Number: EJ1444343
Record Type: Journal
Publication Date: 2023-Feb
Pages: 7
Abstractor: As Provided
ISBN: N/A
ISSN: ISSN-0021-9584
EISSN: EISSN-1938-1328
An Efficient Undergraduate Synthesis of the Exorbitantly Priced Lambert-Eaton Myasthenic Syndrome Drug Amifampridine
Augustine N. Vu; Santana P. Garcia; Jenny H. Tran; Adrian A. Godoy; Joaquin M. Mesa; Cassidy M. DiTirro; Kinsey L. Kotsch; Sarah E. Sullivan; Vincent J. Tavalez; Kateri A. Ahrendt
Journal of Chemical Education, v100 n2 p914-920 2023
An efficient synthesis of the exorbitantly priced Lambert-Eaton myasthenic syndrome drug amifampridine was developed and applied in the second-semester undergraduate organic chemistry laboratory. The two-step synthesis entails a nucleophilic aromatic substitution reaction of commercial 4-chloro-3-nitropyridine with methanolic ammonia to afford 4-amino-3-nitropyridine. Subsequent palladium-catalyzed nitro reduction provides amifampridine in high yield and purity. Amifampridine can alternatively be prepared by advanced undergraduate students in four linear steps beginning with 4-hydroxypyridine. Nitration of 4-hydroxypyridineto 4-hydroxy-3-nitropyridine and subsequent treatment with phosphoryl chloride provides the intermediate 4-chloro-3-nitropyridine, which is then subjected to the S[subscript N]Ar and reduction reactions to cleanly afford amifampridine without the need for column chromatography.
Descriptors: College Science, Undergraduate Study, Organic Chemistry, Science Laboratories, Pharmacology, Scientific Concepts, Concept Formation, Science Instruction
Division of Chemical Education, Inc. and ACS Publications Division of the American Chemical Society. 1155 Sixteenth Street NW, Washington, DC 20036. Tel: 800-227-5558; Tel: 202-872-4600; e-mail: eic@jce.acs.org; Web site: http://pubs.acs.org/jchemeduc
Publication Type: Journal Articles; Reports - Research
Education Level: Higher Education; Postsecondary Education
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A
Grant or Contract Numbers: N/A