Synthesis of tritium, deuterium and carbon-14 labeled (S)-N-ethyl-N-methyl-3-[1-(dimethylamino)ethyl]carbamic acid, phenyl ester, (L)-2,3-dihydroxybutanedioic acid salt (SDZ ENA 713 hta), an investigational drug for the treatment of Alzheimer's disease

Article abstract of DOI:10.1002/(SICI)1099-1344(199708)39:8<651::AID-JLCR14>3.0.CO;2-8

(S)-(-)-N-Ethyl-N-methyl-3-[1-(dimethylamino)ethyl] carbamic acid, phenyl-2-³H-ester, (L)-2,3-dihydroxybutanedioic acid salt was synthesized via directed ortho-metallation methodology. (S)-(-)-N-Ethyl-N-methyl-3-[1-(di-(²H₃)-methylamino)ethyl]carbamic acid, phenyl ester, (L)-2,3-dihydroxybutanedioic acid salt was synthesized from 3-hydroxyacetophenone. The molecule was resolved by classical diastereomeric salt formation and fractional crystallization. The carbon-14 analog, (S)-(-)-N-ethyl-N-methyl-3-[1-(dimethylamino)ethyl-1-(¹⁴C)]carbamic acid, phenyl ester, (L)-2,3-dihydroxybutanedioic acid salt was constructed starting from 3-iodoanisole and featured the enantioselective reduction of a methoxylamine intermediate.