A kind of preparation method of empagliflozin
A technology of empagliflozin and structural formula, which is applied in the field of preparation of key intermediates of empagliflozin, can solve the problems of unsuitability for industrial production and cumbersome operation, and achieve the effects of less impurities, lower impurity content, and shortened production cycle
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0075] Example 1 Preparation of compounds of formula 4
[0076] (1) In a 150 ml three-necked flask, add 2.00 g of the compound of structural formula 1, and then add 4 g of 2-methyltetrahydrofuran and stir to dissolve. The reaction system was protected by nitrogen, and 1.20 g of magnesium turnings and 2.25 g of lithium chloride were added.
[0077] (2) The temperature of the system is raised to 45° C., one iodine grain is added, and it is left to stand for automatic initiation.
[0078] (3) After the reaction is initiated, control the temperature to be 45~55°C, dissolve 18g of the compound of structural formula 1 in 36g of 2-methyltetrahydrofuran, and add it dropwise to the reaction system; Add 1 ml of 10% citric acid solution to quench, take the organic phase HPLC measurement, the relative area of the main peak is greater than or equal to 98%, when the relative area of the chromatographic peak of the compound of structural formula 1 is less than 2%, the reaction is comp...
Embodiment 2
[0089] Example 2 Preparation of compounds of formula 4
[0090] (1) In a 30L reaction kettle, add 300g of the compound of structural formula 1 and 600g of 2-methyltetrahydrofuran. The reaction system was protected by nitrogen, and 179.36 g of magnesium chips and 337.38 g of lithium chloride were added.
[0091] (2) The temperature of the system was raised to 45°C, 1 g of iodine was added, and it was left to stand for automatic initiation.
[0092] (3) After the reaction is initiated, the temperature is controlled to be 45~55°C, and 2.7kg of the compound of structural formula 1 is dissolved in 5.4kg of 2-methyltetrahydrofuran, and added dropwise to the reaction system; after dropping, the mixture is kept at 45~55°C and stirred for 1h; Sampling 1ml, adding 1ml 10% citric acid solution to quench, taking the organic phase HPLC measurement, the relative area of the main peak is greater than or equal to 98%, the relative area of the chromatographic peak of the compound of str...
Embodiment 3
[0106] Example 3 Preparation of empagliflozin
[0107] (1) Take 10.00 g of the compound of structural formula 4 prepared in Example 1, put it in a 100 mL conical flask with stopper, add 15.00 g of acetonitrile and 15.00 g of dichloromethane, shake to dissolve it, and set aside for later use.
[0108] (2) 5.82g of anhydrous aluminum trichloride and 20.00g of dichloromethane were added to the 250mL three-necked flask, cooled to 0~10°C, and 20.00g of acetonitrile was added dropwise through a constant pressure dropping funnel to make the system temperature between 0~30°C °C. After the dropping is completed, 6.53 g of triethylsilane is added, and the equilibrium temperature is adjusted to 15-25°C.
[0109](3) Add the compound solution of structural formula 4 prepared in step 1) dropwise through a constant pressure dropping funnel, and stir for 1-2 hours after the addition, and control the temperature at 15-25° C. in this step.
[0110] (4) When HPLC shows that the compound of f...
PUM
| Property | Measurement | Unit |
|---|---|---|
| wavelength | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More