With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.61869-08-7,(3S,4R)-3-((Benzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine,as a common compound, the synthetic route is as follows.,61869-08-7
203-L isopropanol (water 0. 05% w/v) and 13.5 Kg Paroxetine base are charged simultaneously in a reactor and stirred for 15 min to get clear solution. The solution is filtered through sparkler filter to remove suspended particles. The reactor and sparkler filters are washed with 2 x 13.5-L isopropanol. The filtrate and washing solutions are collected into a glass-lined reactor. To this solution of Paroxetine base a solution of 20% w/v hydrogen chloride in isopropanol is added from addition funnel during 120 minutes at 30-35C to bring the pH of the reaction mass between 3-4 (checked on pH paper), at this pH Paroxetine hydrochloride crystallizes. The slurry is stirred for 15 minutes and then slowly heated to 80-82C, 135 L isopropanol is distilled off at atmospheric pressure and then cooled. The product crystallized out at 45C, which is then further cooled to 30-35C and stirred for 1 hr at this temperature. The product is centrifuged and washed with 2 x 13.5-L isopropanol. The wet cake is then transferred to a vacuum tray dryer. The product is dried at 30-35C for 2 hrs, at 50-55C for 6 hrs and finally at 70-75C for 12 hrs under reduced pressure of 30 mm, reducing isopropanol content to less than 3%. The yield of anhydrous Paroxetine hydrochloride is 13.5 Kg Water content of distillate 0.6% Melting point 116-117C Purity (by HPLC) 99.72% Water (by KFR) 1.48% isopropanol (by GC) 2.4%; Example 2 20 g of Paroxetine base is dissolved in 360-ml isopropanol (water <0.05%). The solution is filtered through filter pad in Buchner funnel. The pad is washed twice with 20-ml isopropanol. To the clear filtrate is added 20% w/v hydrogen chloride solution in isopropanol at 30-35C to bring the pH of the reaction mass between 3-4 (checked on pH paper). Paroxetine hydrochloride is CRYSTALLISED out. The slurry is stirred for 15 minutes and then slowly heated to 80-82C to obtain a clear solution, which is then subjected to distillation for the removal of 200 ml isopropanol at atmospheric pressure. The solution is then cooled and the product crystallised out at 30-35C. Slurry thus obtained is stirred for 1 hr at the same temperature. The product is filtered and washed with 4 x 20-ml isopropanol. The wet cake is dried in vacuum oven at 65C for 4 hrs and between the range 70-75C for 16 hrs under reduced pressure of 30 mm to afford 19.9 g Paroxetine hydrochloride. Melting point 116-117C Water content of distillate 0.55% Purity by HPLC 99.96%, Isopropanol (by GC) 2.96% Water (by KFR) 1.5%; Example 3 20 g of Paroxetine base is dissolved in 360-ml isopropanol (water <0.05%). The solution is filtered through filter pad in Buchner funnel. The pad is washed twice with 20 ml isopropanol. To the clear filtrate is added 20% hydrogen chloride solution in isopropanol at 30-35C to bring the pH of the reaction mass between 3-4 (checked on pH paper). Paroxetine hydrochloride is crystallized out at this pH. The slurry is stirred for 15 min. and then slowly heated to 80-82C to obtain a clear solution, which is then subjected to distillation for removal of 200 ml isopropanol at atmospheric pressure. The solution is then cooled to 30 to 35 C and the product crystallized out. The slurry thus obtained is stirred for 1 hour. The product is filtered and washed with 4 x 20-ml isopropanol. The wet cake is dried in vacuum oven between the range 70-75C for 16 hrs under reduced pressure of 30 mm to afford 19.5 g of Paroxetine hydrochloride. Melting point 116-117C Water content of distillate 0.6% Purity by HPLC 99.96%, Isopropanol (by GC) 2.18% Water (by KFR) 1.46%
The synthetic route of 61869-08-7 has been constantly updated, and we look forward to future research findings.
Reference：
Patent; CADILA HEALTHCARE LIMITED; WO2005/19209; (2005); A2;,
Piperidine – Wikipedia
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