(S)-Bu-HIBO

Chemical Name: 2(S)-Amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid
CAS No. 204863-21-8
项目整合开发状态: Preclinical
项目研究机构: Lundbeck (Originator)
合成路线:Cyclization of oxoester (I) with aqueous hydroxylamine at 0 C gave a mixture of two isoxazoles (II) and (III),which were separated by column chromatography.Methylation of (II) with ethereal diazomethane provided methyl ether (IV).This was regioselectively brominated with Br2 at 50 C to give bromomethyl compound (V).Further treatment with dimethyl acetamidomalonate (VI) and NaOMe in refluxing methanol gave (VII) (1).Then,hydrolysis and decarboxylation of malonate (VII) in refluxing 2 M HCl afforded racemic amino acid (VIII),and subsequent protection with di-tert-butyl dicarbonate gave carbamate (IX).Formation of the salt with (S)-1-phenylethylamine (X) and recrystallization from EtOH-Et2O provided pure (S)-amino acid as the phenylethylamine salt (XI).Free acid was obtained by treatment with acetic acid,and then a reflux in concentrated HBr effected hydrolysis of both methyl ether and carbamate groups to afford the target (S)-amino acid.