Dicloxacillin sodium drug intermediates 2, 6-dichloro toluene synthesis method

摘要

#$%^&*AU2016102198A420170216.pdf#####ABSTRACT Dicloxacillin sodium drug intermediates 2, 6-dichloro toluene synthesis method, comprising the following steps: equipped with a stirrer, a thermometer, a dropping funnel and a reaction vessel was added 500 mL potassium chloride solution with a mass fraction of 40% --- 50% and a certain amount of aqueous solution, the solution temperature was maintained at 85-90C, 1.2mol 2-methyl-3-chloro aniline(2) was added in batches, until the reactant was completely dissolved, maintain the solution temperature to 6--9'C, 1.2-1.6mol potassium nitrite was added dropwise in 200mL aqueous solution, during the process to maintain the solution temperature at 6--8 C, the process was maintained at 30-40min, KI test paper measuring end of the reaction, generating diazonium salt solution (3); 0.3-0.5mol nitrate and a certain amount of nitrite was dissolved in 600-700mL aqueous solution, 500mL potassium chloride solution with a mass fraction of 60-80%was added, the solution was heated to 60 C, generating the chloride salt solution, the diazonium salt (3) solution was slowly added to the chloride salt solution, maintaining the stirring rate at 500 rpm, the addition process was maintained at 30-50min, standing for 2h,the solution to be layered, oil layer washed with acid solution 3-5 times, neutralizing solution 3-5 times, and washed with sodium carbonate solution 2-3 times, sodium bicarbonate solutionwas added last and the solution was maintained at pH 7-8, the water layer was separated, dehydrated with oxidized calcium and distillation, collecting fractions of 180--192'C , ultimately got 2,6-dichloro-toluene.