Method for producing atorvastatin calcium by using micro-reaction device

A technology of atorvastatin calcium and micro-reaction devices, applied in chemical instruments and methods, chemical/physical/physical chemical reactors, chemical/physical/physical chemical processes, etc., can solve difficult problems such as recrystallization and separation, Achieve the effects of easy heat and mass transfer, high selectivity, and small reaction volume

Active Publication Date: 2020-07-03
FUJIAN HAIXI PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The main problem of these two methods in the synthesis of pyrrole rings is that 2-(N-isobutyryl-N-2-(1,3-dioxolane-2)ethyl)amino-p-fluorophenylacetic acid and N, 3-Diphenylpropynamide will form isomers when closing the ring, and the two isomers have similar properties, so it is difficult to separate them by recrystallization
[0014] 5. No amplification effect: batch reactors are often used in fine chemical production

Method used

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  • Method for producing atorvastatin calcium by using micro-reaction device
  • Method for producing atorvastatin calcium by using micro-reaction device
  • Method for producing atorvastatin calcium by using micro-reaction device

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Weigh 20mL of 0.5mol / L hydrochloric acid solution, stir at room temperature to mix evenly to make homogeneous solvent A. Weigh 1.0 g of atorvastatin calcium intermediate L1, dissolve in 20 ml of aqueous methanol (methanol: water = 7: 3), stir at room temperature to mix evenly to form a homogeneous solution B. Weigh 0.8g of sodium hydroxide and dissolve it in 20mL of water, stir at room temperature to make it evenly mixed to make a homogeneous solution C. The homogeneous solution A and the homogeneous solution B are pumped into the Y-shaped mixer at a flow rate of 0.868mL / min respectively, and after mixing, they are passed into the first microreactor with a coil inner diameter of 1mm. The volume of the reactor is 5mL. The temperature is controlled at 40°C, and the reaction residence time is 20min; at the same time, the homogeneous solution C is pumped into the T-type mixer at a flow rate of 0.12mL / min, and after mixing, it is passed into the second microreactor, and the ...

Embodiment 2

[0043] Weigh 20mL of 0.5mol / L hydrochloric acid solution, stir at room temperature to mix evenly to make homogeneous solvent A. Weigh 1.0 g of atorvastatin calcium intermediate L1, dissolve in 20 ml of aqueous methanol (methanol: water = 7: 3), stir at room temperature to mix evenly to form a homogeneous solution B. Weigh 0.8g of sodium hydroxide and dissolve it in 20mL of water, stir at room temperature to make it evenly mixed to make a homogeneous solution C. The homogeneous solution A and the homogeneous solution B are pumped into the Y-type mixer at a flow rate of 0.428mL / min respectively, and after mixing, they are passed into the first microreactor with a coil inner diameter of 1mm. The volume of the reactor is 10mL. The temperature is controlled at 50°C, and the reaction residence time is 20min; at the same time, the homogeneous solution C is pumped into the T-type mixer at a flow rate of 0.12mL / min, and after mixing, it is passed into the second microreactor, and the v...

Embodiment 3

[0045] Weigh 20mL of 0.5mol / L hydrochloric acid solution, stir at room temperature to mix evenly to make homogeneous solvent A. Weigh 1.0 g of atorvastatin calcium intermediate L1, dissolve in 20 ml of aqueous methanol (methanol: water = 7: 3), stir at room temperature to mix evenly to form a homogeneous solution B. Weigh 0.8g of sodium hydroxide and dissolve it in 20mL of water, stir at room temperature to make it evenly mixed to make a homogeneous solution C. The homogeneous solution A and the homogeneous solution B are pumped into the Y-shaped mixer at a flow rate of 0.428mL / min respectively, and after mixing, they are passed into the first microreactor with a coil inner diameter of 1mm. The volume of the reactor is 15mL. The temperature is controlled at 60°C, and the reaction residence time is 20min; at the same time, the homogeneous solution C is pumped into the T-type mixer at a flow rate of 0.12mL / min, and after mixing, it is passed into the second microreactor, and the...

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Abstract

The invention discloses a method for continuously producing atorvastatin calcium by using a micro-reaction device. The production method provided by the invention is simple in process, can realize continuous production, and has relatively high operation safety and selectivity; in addition, since a reaction volume is small and reaction time is short, corrosion to equipment is small; and meanwhile,as a micro-channel reactor has the characteristics of efficient heat and mass transfer capacity and easiness in direct amplification, a reaction conversion rate is high, the obtained atorvastatin calcium is good in quality and low in energy consumption, and the method is an environment-friendly and efficient method for synthesizing atorvastatin calcium.

Description

technical field [0001] The invention relates to the field of synthesis of pharmaceutical intermediates, in particular to a production process for preparing anti-hyperlipidemic drug atorvastatin calcium using a micro-reaction device. Background technique [0002] Atorvastatin calcium (Atorvastatin calcium), the chemical name is (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl )pyrrol-1-yl]-3,5-dihydroxyheptanoic acid calcium salt (2:1) trihydrate, the listed product is its hemi-calcium salt trihydrate, which is sold by the Warner-Lambert company of the United States, and the trade name is Lipitor (LIPITOR), the structural formula is as follows: [0003] [0004] Atorvastatin calcium is an angiotensin Ⅱ (angiotensin Ⅱ) AT1 receptor antagonist. Atorvastatin calcium can reduce the level of cholesterol and lipoprotein in plasma by inhibiting the synthesis of HMG-CoA reductase and cholesterol in the liver. , and by increasing the hepatic LDL receptors on ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/34B01J19/00
CPCC07D207/34B01J19/0093Y02P20/10
Inventor 赖远鸿王如勇郑建加冯岩康心汕
Owner FUJIAN HAIXI PHARMA
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