(R) - (+) - α- Phenylethylamine And (1R, 2S) - (-) - 1,2- Epoxypropyl Phosphonic Acid - (R) - (+) - α- Phenethylamine Salt Synthesis New Technology

As a broad-spectrum antibiotic,fosfomycin occupies an important position in China’s pharmaceutical industry.(1R,2S)-(-)-1,2-epoxypropyl phosphonic acid-(R)-(+)-α-phenylethylamine salt is a key intermediate for the synthesis of fosfomycin.The synthesis process of(R)-(+)-α-phenylethylamine and(1R,2S)-(-)-1,2-epoxypropyl phosphonic acid-(R)-(+)-α-phenylethylamine salt as well as the resolution of racemic α-phenylethylamine was studied based on the problem of enterprises.(R)-(+)-α-phenylethylamine is a widely used chiral resolving reagent of racemic organic acids.Firstly,using D-(-)-tartaric acid as resolving reagent with a programmed cooling crystallization, the resolution process of racemic α-phenylethylamine was studied.The resolving conditions such as the amount of solvent and crystallization temperature were optimized.Under the best condition,(R)-(+)-α-phenylethylamine was obtained in86.5%yield and93.0%ee.Meanwhile,a new kind of tartaric acid recovery method was also developed from the solution of sodium tartrate in THF using sulfuric acid as acidifier.And the D-(-)-tartaric acid was recovered in93.0%yield and99.0%purity.Secondly,the byproduct(S)-(-)-α-phenylethylamine was racemized by KOH catalysis of its imine derivative.Using toluene and dioxane as derivatization and racemization solvent respectively,racemization of(S)-(-)-α-phenylethylamine occurred in86.5%yield of(±)-α-phenylethylamine.A series of H2WO5/C catalyst are prepared from tungstic acid and activated carbon,and its composition and properties were characterized using IR,etc;The catalysis of(1R,2S)-(-)-1,2-epoxypropyl phosphonic acid-(R)-(+)-α-phenylethylamine salt with these catalysts to synthesize(1R,2S)-(-)-1,2epoxypropyl phosphonic acid-(R)-(+)-α-phenylethylamine salt,was successful. After recrystallization from ethanol,the product was obtained with30.0%yield. Moreover the recovery rate of H2WO5/C catalyst is87.0%.The recovered H2WO5/C catalyst kept similar reactivity.The process is simple to operate and the catalyst is easily reactivated.The catalytic reaction of cis propylene phosphate epoxidation using H2WO5/C catalyst proceed as a racemic manner and Et3N can replace part of(R)-(+)-α-phenylethylamine.