Method of preparing letrozole

A technology of letrozole and reaction, which is applied in the field of letrozole preparation, can solve problems such as great influence on yield, difficulty in obtaining potassium tert-butoxide, strong alkalinity of potassium tert-butoxide, etc., and achieve high production efficiency and low price , less side effects

Active Publication Date: 2007-09-12
上海复旦复华药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Potassium tert-butoxide is too alkaline, the reaction is violent, it is difficult to control in large-scale production, the degree of oxidation of the reactants is large, which has a great impact on the yield, and the product is not easy to purify
Moreover, potassium tert-butoxide is difficult to obtain and relatively expensive

Method used

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  • Method of preparing letrozole
  • Method of preparing letrozole
  • Method of preparing letrozole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Add 100 ml of DMF to the reaction flask and dissolve 7.3 g of sodium ethoxide. After stirring, 100 ml of DMF solution containing 10 g of Compound I was slowly added, and the reaction temperature was controlled at 10°C. After the addition was complete, stirring was continued for one hour at room temperature. After stirring, 50 ml of a DMF solution containing 8 g of p-fluorobenzonitrile was slowly added at room temperature. Stirring was continued for half an hour after the addition was complete. The pH was adjusted to 7 with concentrated hydrochloric acid, and the solvent was removed under reduced pressure. An appropriate amount of water was added, extracted three times continuously with dichloromethane, and the organic phases were combined and washed with saturated brine. After drying over magnesium sulfate, the solvent was distilled off to obtain a crude product. Recrystallization with ethyl acetate gave 12.8 g of pure product with a yield of 82.7%. Product melting...

Embodiment 2

[0030] Add 100 ml of DMF to the reaction flask, and dissolve 12.1 g of potassium tert-butoxide. After stirring, 100 ml of DMF solution containing 10 g of Compound I was slowly added dropwise, and the reaction temperature was controlled at 10°C. After the addition was complete, stirring was continued for one hour at room temperature. After stirring, 50 ml of a DMF solution containing 8 g of p-fluorobenzonitrile was slowly added dropwise at room temperature. Stirring was continued for half an hour after the addition was complete. The pH was adjusted to 7 with concentrated hydrochloric acid, and the solvent was removed under reduced pressure. An appropriate amount of water was added, extracted three times continuously with dichloromethane, and the organic phases were combined and washed with saturated brine. After drying over magnesium sulfate, the solvent was distilled off to obtain a crude product. Recrystallization with ethyl acetate gave 7.8 g of pure product with a yield...

Embodiment 3

[0032]Add 100 ml of DMF to the reaction flask and dissolve 7.3 g of sodium ethoxide. After stirring, 100 ml of DMF solution containing 10 g of Compound I was slowly added, and the reaction temperature was controlled at 20°C. After the addition was complete, stirring was continued for one hour at room temperature. After stirring, 50 ml of a DMF solution containing 8 g of p-fluorobenzonitrile was slowly added at room temperature. Stirring was continued for half an hour after the addition was complete. The pH was adjusted to 7 with concentrated hydrochloric acid, and the solvent was removed under reduced pressure. An appropriate amount of water was added, extracted three times continuously with dichloromethane, and the organic phases were combined and washed with saturated brine. After drying over magnesium sulfate, the solvent was distilled off to obtain a crude product. Recrystallized from ethyl acetate to obtain 10.2 g of pure product with a yield of 66%. Product melting ...

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Abstract

This invention provides a preparation method for preparing pure Letrozole, which takes sodium ethoxide as the catalyst, in which, the reaction temperature is not higher than 30deg.C. Advantages: the alkali of sodium ethoxide is weak and reacts mildly, and its conditions in both labs and production are simple and easy to be got.

Description

technical field [0001] The invention relates to a preparation method of letrozole, in particular to a process improvement of the preparation method of letrozole. Background technique [0002] Endocrine therapy is one of the main means of treating breast cancer. In 1896, British scholar Beatsom used oophorectomy to treat advanced breast cancer before menopause, creating the history of endocrine therapy for breast cancer. After the estrogen receptor (ER) was successfully isolated in the late 1960s, endocrine therapy for breast cancer was selectively used in ER-positive cases, and the therapeutic effect was significantly improved. Oral tamoxifen 20 mg per day has been used as a routine method of endocrine therapy for breast cancer, and is widely used in the treatment of breast cancer at various stages. In the 1990s, the emergence of the third generation of highly selective aromatase inhibitors brought endocrine therapy into a new era. [0003] Aromatase, also known as estroge...

Claims

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Application Information

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IPC IPC(8): C07D249/08
Inventor 陈土耀
Owner 上海复旦复华药业有限公司
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