METHOD OF PRODUCING PROPOFOL ACTIVE PHARMACEUTICAL SUBSTANCE Russian patent published in 2024 - IPC C07C39/06 C07C37/74 

FIELD: chemistry; pharmaceutics.

SUBSTANCE: invention refers to chemistry and pharmaceutics, namely to a method for preparing the active pharmaceutical substance propofol, which can be used for producing medicinal preparations having analgesic action. Method involves three steps. At the first step, alkylation of 4-hydroxybenzoic acid is carried out in the presence of concentrated sulfuric acid at temperature of 50 ± 1 °C for 4–5 hours, after which the reaction mass is cooled, cyclohexane and water are added, the mixture is stirred and a suspension of product of 3,5-diisopropyl-4-hydroxybenzoic acid is obtained, which is filtered, the precipitate on the filter is washed with water and dried. At the second step, decarboxylation of 3,5-diisopropyl-4-hydroxybenzoic acid, including addition of 3,5-diisopropyl-4-hydroxybenzoic acid to ethylene glycol and sodium hydroxide in the reactor while stirring and blowing the reactor with a nitrogen current, after which the reaction is continued at an excess pressure of nitrogen at a temperature of the reaction mass of 160–170 °C for 3–5 hours, after said time, the reaction mixture is cooled, extraction is carried out by adding toluene and water, mixing, then the mixer is stopped, and the reaction mass is allowed to separate, the upper layer is collected in a collector, extraction is repeated, then NaCl solution is added to the extract, the mixture is stirred, and the mixture is allowed to exfoliate, the upper layer containing toluene and propofol is poured into a distillation vessel, toluene is distilled off to obtain technical propofol. At the third stage, technical propofol is purified by vacuum distillation in a nitrogen atmosphere.

EFFECT: method enables to obtain propofol of high degree of purity, reduce the duration of the process of producing propofol, and the processes are easily scaled without significant change in process parameters.

1 cl, 1 tbl, 4 ex