preparation method of 2-ethylbutyl ((s)-(pentafluorophenoxy)(phenoxy)phosphoryl)-l-alanine ester_industrial additives

background and overview^[1]

2-ethylbutyl ((s)-(pentafluorophenoxy)(phenoxy)phosphoryl)-l-alanine ester is a key intermediate of remdesivir (gs-5734). remdesivir: remdesivir (gs-5734) was developed by gilead sciences in the united states. it is a nucleoside rna-dependent rna polymerase (rdrp) competitive inhibitor. its triphosphate nucleotide product remdesivir -tp can compete with rdrp for the substrate atp and therefore can interfere with viral vrna synthesis. rdrp is an rna polymerase widely distributed in positive-stranded and double-stranded rna viruses. therefore, remdesivir has a certain inhibitory effect on filoviruses (ebola, etc.), arenaviruses (lassa fever virus, etc.), coronaviruses (sars, 2019-ncov, etc.), and has a certain inhibitory effect on covs represented by mers. higher inhibitory activity.

preparation^[1]

dissolve phenyl dichlorophosphate (50g, 0.24mol) in 200ml tetrahydrofuran, add pentafluorophenol (43.6g, 0.24mol), add triethylamine (72.7g, 0.72mol) dropwise, and raise the temperature to 35°c stir and react for 4 hours, add l-alanine-(2-ethylbutyl) ester hydrochloride (50.4g, 0.24mol) in batches, stir and react for 2 hours; filter after the reaction, and use saturated sodium chloride solution for the filtrate wash twice, dry over anhydrous magnesium sulfate, concentrate under reduced pressure until thick, add a mixed solvent of ethyl acetate and n-hexane, raise the temperature to dissolve, cool to 0°c and crystallize for 2 hours, filter, and dry the solid in vacuum. compound d, 2-ethylbutyl ((s)-(pentafluorophenoxy)(phenoxy)phosphoryl)-l-alanine ester, was obtained with a yield of 72% (purity 98.3%).