Preparation Of Finasteride By Iodination, Oxidation Reaction Using F9and Preparation Of3-methylcyclohexanone Catalyzed By Palladium

Finasteride is a type of5α-2reductase inhibitors, which mainly used for thetreatment of prostatic hyperplasia, prostate cancer, male hair loss disease, the blood inthe urine after urethra resection of the prostate. It has obtained the good curative effectin clinic. Due to the increasing of market demand, it has very good applicationprospect and development potential. But reported finasteride preparation methods allexist process complex, poor safety, severe pollution and high cost. Thereforedeveloping a simple process, high yield, good quality, clean production technology tomeet the demand for finasteride has important significance. This article mainly aims atdefects of traditional technology, researching a new method for preparing highly purefinasteride, which comprises two steps of reaction. The first step usedihydrofinasteride as a starting material by reacting with iodine to obtain2-iodo-androstane. The second step is by reacting2-iodo-androstane with an oxidizingagent to form finasteride. In the study, we explored the effect of various factors for thetwo steps of reaction and get to the best reaction conditions. Using this technology,highly pure finasteride can be synthesised in very mild conditions, the materialsaccessible, convenient manipulation, friendly to environment.Although the iodination reaction has been reported, the yield is low,post-processing complexity, directly adding2-iodo-androstane to the next step reactionwithout purification, increasing the difficulty of purification of the final product. Weimprove the iodination process to optimize the reaction solvent, reaction temperature,simplify the operation, using the appropriate solvent to purify the F9-I, unreacted rawmaterials recycling, high yield to obtain the high purity of the product. The resultsprove that the best reaction conditions of the first step is: methylene chloride assoivent, triethylamine as acid-binding agent, joining trimethylchlorosilane at-15℃,30min of stirring, temperature at-5~0℃,1:1.5dihydrofinasteride and iodine,4h ofstirring. After the reaction, sodium thiosulfate was used to quenching. Under the bestreaction conditions, yield of2-iodo-androstane can reach97%. After recrystallizationpurification, the purity is more than99.7%.In the oxidation elimination reaction, we study the different oxidant effects forthe reaction, at last to choose metachloroperbenzoic acid and peracetic acid asoxidizing agent. The best reaction conditions is: tetrahydrofuran as soivent,metachloroperbenzoic acid as oxidizing agent,1:0.82-iodo-androstane and oxidizing agent, room temperature,20h of stirring. Under the best reaction conditions, yield offinasteride is97%, the purity is more than99.6%. The best reaction conditions of usingperoxyacetic acid to prepare finasteride is: tetrahydrofuran as soivent, peroxyaceticacid as oxidizing agent,1:22-iodo-androstane and oxidizing agent, room temperature,24h of stirring. Under the best reaction conditions, yield of finasteride is96%, thepurity is more than99.8%.3-methyl cyclohexanone is an important organic solvent and organic chemicalintermediates. It has a wide range of applications in medicine, spices, organic finechemical synthesis. At present, which mainly use3-methyl-2-cyclohexene-1-ketone tosynthesize. But the preparation methods of3-methyl-2-cyclohexene-1-ketone haveshortages, such as a low yield, reagents and catalysts expensive. In this article, westudy a new method to prepare3-methyl cyclohexanone, which use3-methyl phenol asstarting material under the Pd/C-catalyzed hydrogenation to generate3-methylcyclohexanol and3-methyl cyclohexanone. The best conditions is:0.003%of sodiumcarbonate, dosage of3.0%Pd/C, temperature at160℃, the pressure at6.0MPa,4.0hof stirring. The raw material of3-methyl phenol can completely convert. So afterhydrogenation reduction, we do not need separate raw material. Based on the rawmaterial of3-methyl phenol100%conversion, the yield of3-methyl cyclohexanone ashigh as possible, when oxidizing3-methyl cyclohexanol to generate3-methylcyclohexanone, we can reduce the amount of oxidant.