Synthesis method of phentermine hydrochloride

Abstract

The invention discloses a method for preparing phentermine hydrochloride. The method for preparing the phentermine hydrochloride is characterized in by comprising the following steps: adding dimethyl benzyl carbinol serving as raw material into a mixed solution of acetic acid and an organic solvent, then dropwise adding sulphuric acid serving as a catalyst, stirring for reaction, then adding water until the solution is turbid, adding aqueous alkali for regulating pH to 6-8, and then carrying out reduced-pressure suction filtration to obtain N-(1,1-dimethyl-phenethyl) acetamide; then dissolving N-(1,1-dimethyl-phenethyl) acetamide into an organic solvent, carrying out heating reflux in the presence of inorganic strong alkali solid serving as an acid-binding agent, and cooling to room temperature; adding water, stirring and extracting a product; drying with an anhydrous drying agent overnight; removing the solid, carrying out reduced pressure distillation on filtrate by adopting a water pump, so as to obtain phentermine free alkali; then dissolving with the organic solvent; adding hydrochloric acid under an ice bath condition or introducing dry hydrogen chloride gas, then stirring and carrying out suction filtration to obtain the phentermine hydrochloride. The method for preparing the phentermine hydrochloride has the advantages of high yield, low cost and no adoption of column chromatography and is suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a synthesis method of phentermine hydrochloride. technical background [0002] In recent years, with the improvement of people's living standards and the increase of work pressure, obesity has increasingly become a killer of people's health. Obesity and metabolic syndrome (cardiovascular risk factors, including hypertension, fat metabolism disorder and insulin resistance ) are closely related and can shorten lifespan. [0003] Phentermine was once approved by the US Food and Drug Administration (FDA) as an appetite suppressant in 1997, but it was discontinued due to side effects such as valvular heart disease. In recent years, with the continuous development of drug research, it has been found that phentermine hydrochloride The compound preparation composed of topiramate has good tolerance and safety, and its weight loss effect is twice that of orlistat. On July 17, 2012, the US FDA officially approved Qsymia (phentermine a...

AI Technical Summary

Problems solved by technology

[0007] (1) In the first step of the synthesis process, it is necessary to use a strong base such as NaH, sodium alkoxide, etc. to remove the α-H of the nitro-ortho position, the synthesis cost is high, and the reaction time is long, and 1mol of 1-nitroethylbenzene is completely reacted The time is 27h, which greatly limits the industrial production of phentermine

[0008] (2) In the second step of the synthesis process, under the condition of palladium carbon as a catalyst, high-pressure hydrogenation is required, which requires high equipment and increases production costs.

[0009] (3) In the third step of the synthesis process, concentrated hydroiodic acid is used to remove the hydroxyl group of the aryl benzyl position. This reaction needs to be carried out under high temperature conditions, and the yield is not high, thereby greatly slowing down the reaction time and reducing production efficiency.

[0010] Overall, this method requires expensive reagents such as sodium hydrogen, sodium alkoxide, and hydroiodic acid, and the overall reaction conditions are relatively harsh, so it is not suitable for large-scale industrial production

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