Preparation method of rosuvastatin calcium
A technology of rosuvastatin calcium and rosuvastatin, which is applied in the field of medicinal chemistry, can solve the problems of high impurity diastereomer, difficulty in reduction or removal, etc. The effect of reducing material introduction
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[0028] The preparation method of compound A (reference publication number is the U.S. patent of US20050124639), concrete steps are as follows:
[0029] (1) Put 104g of potassium carbonate, 600ml of dimethyl sulfoxide, and 170g of TPPBr([4-(4-fluorophenyl)-6-isopropyl BFA ((4R-cis)-6-formyl-2,2-dimethyl -1,3-dioxane-4-tert-butyl acetate), adjust the temperature to 70~75°C, react for 2h, monitor the reaction progress with TLC;
[0030] (2) Cool down to 25°C to 35°C, add 1000ml of toluene to dilute, and stir for 30min; filter, add 1000ml of water to the filtrate, stir for 30min, let stand to separate layers, wash the organic layer with 2×1000ml of water, and control the temperature at 50°C to Concentrate under reduced pressure at 70°C; add 750ml of absolute ethanol to the concentrated solution, dissolve at 55-60°C and keep warm for 30 minutes, cool down to 25°C-30°C and stir to precipitate solids, then cool to 11°C and stir to crystallize for 30 minutes, filter with suction, and...
Embodiment 1
[0033] A preparation method of rosuvastatin calcium salt, the specific steps are as follows:
[0034] (1) Protect from light, N 2 Under protective conditions, add compound A 20g (0.0346mol, the structural formula of compound A is: ), acetonitrile 140ml, under the condition of 35~40℃, add dropwise 45ml of hydrochloric acid solution with a concentration of 0.05mol / L, stir for 4h, remove the hydroxyl protecting group (acetonide), cool down to 20~25℃, slowly add dropwise the concentration of 60ml of 5% sodium hydroxide solution was stirred, and the ester was subjected to alkaline hydrolysis for 2 hours to obtain rosuvastatin sodium salt solution. The structural formula of rosuvastatin sodium salt was:
[0035] (2) Concentrate the product of step (1) under reduced pressure to remove the solvent, add 80ml of purified water, stir to dissolve, adjust the pH value to 3-4 with 0.1mol / L hydrochloric acid solution, then extract and separate with 70ml of ethyl acetate, organic The lay...
Embodiment 2
[0038] A preparation method of rosuvastatin calcium salt, the specific steps are as follows:
[0039] (1) Protect from light, N 2 Under protective conditions, add compound A 20g (0.0346mol, the structural formula of compound A is: ), acetonitrile 140ml, under the condition of 35~40℃, add 45ml of hydrochloric acid solution with a concentration of 0.05mol / L dropwise, stir for 3h, remove the hydroxyl protecting group (acetonide), lower the temperature to 20~25℃, slowly add the concentration of 60ml of 5% sodium hydroxide solution was stirred, and the ester was subjected to alkaline hydrolysis for 1 hour to obtain rosuvastatin sodium salt solution. The structural formula of rosuvastatin sodium salt was:
[0040] (2) Concentrate the product of step (1) under reduced pressure to remove the solvent, add 80ml of purified water, stir to dissolve, adjust the pH value to 3-4 with 0.1mol / L hydrochloric acid solution, then extract and separate with 70ml of ethyl acetate, organic The la...
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