Method for preparing 19- nor-4-androstene-3, 17-diketone

A technology of androstene and diketone, which is applied in the field of chemical synthesis of steroid hormone drugs, can solve the problems of long route, high cost, and large environmental pollution, and achieve the effects of high yield, short synthesis steps, and low price

Active Publication Date: 2015-04-08
HUNAN NORCHEM PHARMACEUTICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing preparation method of 19-nor-4-androstene-3,17-dione is based on the saponin containing four steroid paren

Method used

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  • Method for preparing 19- nor-4-androstene-3, 17-diketone
  • Method for preparing 19- nor-4-androstene-3, 17-diketone
  • Method for preparing 19- nor-4-androstene-3, 17-diketone

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preparation example Construction

[0025] The preparation method of the present invention specifically comprises the following steps:

[0026] (1) Grignard reaction

[0027] (a) Under the protection of nitrogen, put magnesium into the first organic solvent at room temperature, add the ketal solution dropwise, and complete the dropwise addition in 4h-8h. After the dripping is completed, keep the temperature for 2h-4h, and then cool down naturally to 0°C for later use. Grignard reagent. In this step, the first organic solvent is anhydrous ether and / or tetrahydrofuran, preferably anhydrous ether; in the ketal solution, the ketal is 2-(3-chloropropyl)-2,5,5-tri Methyl-1,3-dioxane, 2-(3-bromopropyl)-2,5,5-trimethyl-1,3-dioxane or 2-(3- iodopropyl)-2,5,5-trimethyl-1,3-dioxane, more preferably 2-(3-chloropropyl)-2,5,5-trimethyl-1, 3-dioxane, the solvent is an ether solvent, preferably tetrahydrofuran; the reaction temperature during the heat preservation reaction is 20°C to 60°C, preferably 20°C to 40°C. The mass ...

Embodiment 1

[0036] A preparation method of 19-nor-4-androstene-3,17-dione of the present invention, the preparation method uses compound I as a raw material, undergoes Grignard reaction, oxidation and ring closure reaction, reduction and ring closure reaction Prepared, the reaction scheme is as follows:

[0037]

[0038] (1) Grignard reaction

[0039] (a) At room temperature, under the protection of nitrogen, add 70ml of anhydrous ether and 8.5g of magnesium to a clean and dry 500ml four-necked round-bottomed flask equipped with a thermometer, a reflux condenser, and mechanical stirring, and heat up to 30°C. After the reaction starts, Start to drop the previously prepared 60g of ketal (specifically 2-(3-chloropropyl)-2,5,5-trimethyl-1,3-dioxane) and 50ml of tetrahydrofuran mixture , 5 to 6 hours after dripping, then keep warm for 3 hours, stir naturally for 4 hours, cool down to 0 degrees for later use, and obtain the Grignard reagent.

[0040] (b) Under nitrogen protection, add 175m...

Embodiment 2

[0048] A preparation method of 19-nor-4-androstene-3,17-dione of the present invention, the preparation method uses compound I as a raw material, undergoes Grignard reaction, oxidation and ring closure reaction, reduction and ring closure reaction Prepared, the reaction scheme is as follows:

[0049]

[0050] The preparation method comprises the following steps:

[0051] (1) Grignard reaction

[0052] (a) At room temperature, under the protection of nitrogen, add 130ml of anhydrous ether and 17g of magnesium to a clean and dry 100ml four-necked round-bottomed flask equipped with a thermometer, a reflux condenser, and mechanical stirring, and heat up to 30°C. After the reaction starts, start 20 g of the ketal compound (specifically 2-(3-bromopropyl)-2,5,5-trimethyl-1,3-dioxane) prepared before was added dropwise and kept for 2 hours. Add 120g of ketal and 100ml of tetrahydrofuran dropwise, finish dropping in 5-6 hours, keep warm for 3 hours, stir naturally for 4 hours, add...

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Abstract

The invention provides a method for preparing 19- nor-4-androstene-3, 17-diketone. The preparation method comprises the following step: with a compound I as a raw material, carrying out a Grignard reaction, an oxidation and ring-closure reaction and a reduction and ring-closure reaction, and the reaction route is shown as follows. The starting raw material of the preparation method is relatively cheap, the product yield is high and the production cost can be saved. The formula is described in the description.

Description

technical field [0001] The invention relates to a chemical synthesis method of a steroid hormone drug, in particular to a preparation method of 19-nor-4-androstene-3,17-dione (ie, 4 substances). Background technique [0002] 19-nor-4-androstene-3,17-dione is an important intermediate for the synthesis of norethindrone and other drugs. Compared with other intermediates, 19-nor-4-androstene-3 , 17-diketones have a simple route for synthesizing the above-mentioned contraceptives, high yield, low cost and high market demand. However, the existing preparation method of 19-nor-4-androstene-3,17-dione is based on saponin containing four steroid parent rings, which is finally made into acidic Decarboxylation, this method has a long route, high cost, and great environmental pollution. Contents of the invention [0003] The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art, and to provide a 19-nor-4-androstene-3,17-bis Method...

Claims

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Application Information

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IPC IPC(8): C07J1/00
CPCC07J1/0011
Inventor 刘喜荣曾春玲
Owner HUNAN NORCHEM PHARMACEUTICAL CO LTD
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