Gliquidone synthesis

Yield:33342-05-1 80%

Reaction Conditions:

Stage #1:4-<2-(3,4-Dihydro-7-methoxy-4,4-dimethyl-1,3-dioxo-2(1H)-isochinolyl)ethyl>benzolsulfonamid with potassium carbonate at 40; for 0.5 h;
Stage #2:Cyclohexyl isocyanate at 90; for 4.5 h;Reagent/catalyst;Temperature;

Steps:

1 Example 1: A method of preparing gliquidone
Isoquinoline (30 g, 74.6 mmol), solvent 2,5-dimethyltetrahydrofuran (300 mL) and anhydrous potassium carbonate (21 g, 151.9 mmol) were sequentially added to a 500 mL reaction flask. Open the stirring and heating, incubated at 40 °C for 30 minutes, and then slowly added cyclohexyl isocyanate (11.2g, 89.5mmol), the control was added dropwise over about 30 minutes after completion of the dropping temperature was raised, 90 °C Heated to reflux for 4 hours. The solvent 2,5_ dimethyltetrahydrofuran was recovered under reduced pressure to give a white solid. To the reaction flask was added 200mL water, hydrochloric acid was slowly added dropwise to adjust PH = 3, cooled to 0-5 °C and stirred for 1 hour, filtered to give crude gliquidone, a yield of 98%. The resulting gliquidone crude product into 5L of the three-necked flask to the bottle was added 3L of methanol, heated to 40 °C, the system was added ammonia / methanol, adjust the pH to 3, the gliquidone Crude product completely dissolved, and then continue to add 3g of neutral alumina and 3g silica gel (200-300 mesh), the use of alumina with silica gel completely adsorbed impurities in the system. 40 °C under stirring for 2 hours, filtered, the filtrate was adjusted with 3 M hydrochloric acid PH = 3, lower the temperature, 0-5 °C under agitation crystallization 4 hours. Filter, filter cake were washed with water, ethanol. 40 °C under vacuum for 12 hours to give a white granular solid, that is, gliquidone. Purity 99.75%, yield 80%.

References:

Tianjin Hengbida Chemical Synthetic Wu Co., Ltd.;Zhao Xin;Zhang Zhiqiang;Wang Kai;Li Lianqi;Ren Xiaofeng;Li Guo;Song Jinjin;Zhao Zhao;Yang Xin CN106316950, 2017, A Location in patent:Paragraph 0032-0054

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