A NEW SIMPLIFIED NETHOD FOR THE SYNTHESIS OF MUSCIMOL (5-AMINOMETHYL-3-HYDROXYISOXAZOLE)

A new and convenient method for the synthesis of muscimol (1) from reaaily available 5-hydroxymethyl-3-hydroxyisoxazole (Ⅱ) was investigated. Without protection of the 3-hydroxy group, Ⅱ was Converted to 5-chloromethyl-3-hydroxy isoxazole (Ⅲ) by direct treatment with thionyl chloride in 75% yield, mp 100～102℃. It was a key step for the production of Ⅰ. The intermediate Ⅲ was aminated to the title compound with agueous ammonia in the presence of ammonium carbonate at 60～70℃ under atmospheric pressure. Thepure product was obtained through fractional crystallization, and the conventional purification step with ion exchange resin was omitted. The melting point of purified compound Ⅰ, 178.9℃ (d), was identical with that synthesized by Gagneux et al₍₃₎. Yield of the pure product was 30～40%. It was also identified by IR-, MS-spectroscopy and elemental analysis as well as some biological tests.