RS-132943

Chemical Name: 3(S)-(4-Bromo-2,6-dimethylphenoxymethyl)-1-methylpiperidine hydrochloride
CAS No. 214148-23-9, 214148-32-0 (free base, undefined isomer), 214149-35-6 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Roche Bioscience (Originator)
合成路线:Racemic ethyl 3-piperidinecarboxylate (Ia,Ib) was resolved with D-(-)-tartaric acid in EtOH to afford the (S)-piperidine tartrate salt (II).After protection of (II) as the N-Boc derivative (III) by treatment with di-tert-butyl dicarbonate and NaOH,reduction of the carboxylate group of (III) by means of LiBH4 provided alcohol (IV).Subsequent coupling of (IV) with 4-bromo-2,6-dimethylphenol (V) under Mitsunobu conditions provided ether (VI).The N-Boc protecting group of (VI) was then cleaved employing trifluoroacetic acid to give piperidine (VII).Finally,Eschweiler-Clarke methylation using formaldehyde and formic acid furnished the corresponding N-methyl piperidine,which was isolated after conversion to the hydrochloride salt.