Related Products of 132813-14-0 , The common heterocyclic compound, 132813-14-0, name is 2-Chloro-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine, molecular formula is C17H17ClFN, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
The inside of a 200 mL flask was placed under a nitrogen atmosphere, and 33.5 mL of toluene and 5.91 g (51.77 mmol) of 1-ethylpiperazine were added and stirred. After cooling to 10 C, 5.00 g (17.26 mmol) of 2-chloro-4- (4-fluorophenyl) -5,6,7,8,9,10-hexahydrocyclo octa [b] pyridine and 1.99 g (20.71 mmol) of sodium-tert-butoxide were added. After reducing the pressure at 100 hPa or less and stirring for 2 minutes, the operation of restoring pressure with nitrogen was repeated 5 times. After adding 0.0775 g (0.345 mmol) of palladium (II) acetate and 0.2715 g (1.035 mmol) of triphenylphosphine, the mixture was depressurized at 100 hPa or less, stirred for 2 minutes, and then pressure restoration with nitrogen was performed three times, and the mixture was stirred under 70 C for 7 hours. The reaction solution was cooled to room temperature, 50 mL of water was added little by little, and after stirring for 30 minutes, the precipitate was removed by filtration using phi 40 mm Kiriyama funnel mounted with 2.50 g of Celite, and washed twice with 10 mL of toluene . The obtained filtrate was transferred to a 300 mL separatory funnel and the aqueous layer was removed (pH 13.0). Water (50 mL) was added to the organic layer, shaken vigorously for 2 minutes, allowed to stand for 10 minutes, and the aqueous layer was removed. This washing operation was repeated until the aqueous layer pH was 9 or less, to obtain a blonanserine toluene solution (49.86 g). Blonanserin content: 5.67 g, reaction yield: 89.12%, HPLC purity: 87.70%.49.86 g (blonanserin 5.67 g, 15.43 mmol) of the toluene solution of bronan serine obtained in Step 1 was added to a 200 mL flask, 25 mL of toluene was added, and the mixture was added at 50 C. and 50 to 70 hPa The mixture was concentrated under reduced pressure in an amount corresponding to toluene to prepare 54.64 g of a toluene solution of blonanserin.Separately from the above, a 200 mL flask was prepared and under a nitrogen atmosphere, 50 mL of ethanol was added and the mixture was cooled to 10 C., and 3.38 g (34.51 mmol) of 98% sulfuric acid was slowly added dropwise thereto to prepare a sulfuric acid ethanol solution .The bronan serine toluene solution transferred to the 100 mL dropping funnel was slowly added dropwise to the stirred ethanol sulfuric acid solution while keeping the inside of the system at 0 to 10 C. and stopped when 1/5 amount was added dropwise, and 0.5 mg of bronanserin sulfate seed crystals The mixture was stirred for 30 minutes when solid precipitation was confirmed.Thereafter, the remaining 4/5 amount of dropwise addition of the toluene solution of bronan serine was restarted, and after completion of the dropwise addition, it was washed with 5 mL of toluene and stirred at 0 to 10 C. for 30 minutes.The precipitated solid was filtered with a phi 40 mm Kiriyama funnel, the cake was washed twice with 25 mL of cold toluene and dried on a Kiriyama funnel for 30 minutes to obtain 8.67 g of a light red solid.HPLC purity: 99.40%.Step 3 Recrystallization of Blonanserin Sulfate A300 mL flask was placed under a nitrogen atmosphere, 8.66 g (15.36 mmol) of the bronnan serine sulfate obtained in Step 2, 125 mL ethanol and 2.50 mL water were added and heated to reflux to obtain a uniform solution .The mixture was cooled to an internal temperature of 10 C. over 2 hours and 30 minutes and stirred at 0 to 10 C. for 30 minutes.The precipitated solid was filtered with a phi 40 mm Kiriyama funnel, the cake was washed twice with cold ethanol 15 mL, and dried on a Kiriyama funnel for 30 minutes to obtain 6.76 g of an off white solid.HPLC purity: 99.98%.
The synthetic route of 132813-14-0 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; DAI NIPPON PRINTING COMPANY LIMITED; YONEYAMA, TAKUYA; ONOZAWA, TAKASHI; (10 pag.)JP2018/127406; (2018); A;,
Pyridine – Wikipedia,
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