Synthesis method of medroxyprogesterone acetate

The technology of a methadone and a synthetic method, which is applied in the field of pharmaceutical chemical synthesis, can solve the problems of high cost and low yield, and achieve the effects of reducing processing cost, good production safety, and easy recycling and reuse

Inactive Publication Date: 2013-02-06
BAOJI KANGLE BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] In this production process, the etherification reaction yield is 95% to 98%, the hydrogenation reaction yield is 85% to 88%, the refining yield is 90% to 94%, and the total yield is 72% to 82%. Low; in the second step of catalytic hydrogenation, the catalyst used is a noble metal palladium catalyst, and the cost is relatively high

Method used

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  • Synthesis method of medroxyprogesterone acetate
  • Synthesis method of medroxyprogesterone acetate
  • Synthesis method of medroxyprogesterone acetate

Examples

Experimental program
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Effect test

Embodiment 1

[0052] Step 1. Using 17α-hydroxyprogesterone as a raw material, react with ethylene glycol under the catalysis of p-toluenesulfonic acid to obtain a ketal product through ketal reaction:

[0053] 101. In a clean 2000L enamel reaction kettle, pump in 1150kg of fresh benzene, 440kg of ethylene glycol, put in 50kg of 17α-hydroxy progesterone, stir, azeotropically distill off water for 1.5h, then add 2.2kg of toluenesulfonic acid into the reaction kettle , continue azeotropic distillation to remove water for 1 hour, and reflux at 100°C for 9 hours; then add 7.5kg of pyridine to the reactor to terminate the reaction, let it stand after cooling, discard the upper solution, and use 500kg of carbonic acid with a mass percentage concentration of 5% for the lower solution After washing with sodium hydrogen solution, wash with water until neutral;

[0054] 102. Concentrate under reduced pressure the lower layer solution washed to neutral in 101 to obtain a concentrated solution, add 400k...

Embodiment 2

[0073] Step 1. Using 17α-hydroxyprogesterone as a raw material, react with ethylene glycol under the catalysis of p-toluenesulfonic acid to obtain a ketal product through ketal reaction:

[0074] 101. In a clean 2000L enamel reaction kettle, pump in 1150kg of fresh benzene, 400kg of ethylene glycol, put in 50kg of 17α-hydroxyprogesterone, stir, azeotropically distill off water for 1 hour, add 2kg of toluenesulfonic acid into the reaction kettle, continue Azeotropic distillation to remove water for 1.5h, reflux reaction at 110°C for 8h; then add 5kg of pyridine to the reaction kettle to terminate the reaction, let it stand after cooling, discard the upper layer solution, and use 400kg mass percentage concentration of 7% sodium bicarbonate for the lower layer solution After washing with the solution, wash with water until neutral;

[0075] 102. Concentrate under reduced pressure the lower layer solution washed to neutral in 101 to obtain a concentrated solution, add 300kg of met...

Embodiment 3

[0094] Step 1, using 17α-hydroxyprogesterone as a raw material, reacting with ethylene glycol through ketal reaction under the catalysis of p-toluenesulfonic acid to obtain a ketal product:

[0095] 101. In a clean 2000L enamel reaction kettle, pump in 1150kg of fresh benzene, 500kg of ethylene glycol, put in 50kg of 17α-hydroxyprogesterone, stir, azeotropically distill off water for 2 hours, then add 2.5kg of toluenesulfonic acid into the reaction kettle, Continue azeotropic distillation to remove water for 0.5h, and reflux reaction at 110°C for 8h; then add 10kg of pyridine to the reaction kettle to terminate the reaction, let it stand after cooling, discard the upper layer solution, and use 600kg mass percentage concentration of 3% hydrogen carbonate for the lower layer solution After washing with sodium solution, wash with water until neutral;

[0096] 102. Concentrate under reduced pressure the lower layer solution washed in 101 to neutrality to obtain a concentrated solu...

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Abstract

The invention discloses a synthesis method of medroxyprogesterone acetate. The method comprises the following steps of: 1) enabling 17 alpha-hydroxyprogesterone and ethylene glycol to perform ketalation under the catalysis of para-toluenesulfonic acid to obtain a ketal; 2) enabling the ketal to perform epoxidation reaction under the action of a peroxyacetic acid solution of anhydrous sodium acetate to obtain an epoxide; 3) enabling the epoxide and methylmagnesium bromide to perform Grignard reaction, and then performing hydrolysis reaction by dilute sulphuric acid to obtain a Grignard matter; 4) performing hydrolysis on the Grignard matter by glacial acetic acid to perform deprotection so as to obtain 5 alpha, 17 alpha-dihydroxy-6 beta-methyl progesterone; 5) performing hydrogenation translocation reaction under the action of hydrogen chloride to obtain 6 alpha-methyl-17 alpha-hydroxyprogesterone; and 6) enabling the 6 alpha-methyl-17 alpha-hydroxyprogesterone to perform acetylation reaction with acetic acid and acetic anhydride so as to obtain the medroxyprogesterone acetate. During the reaction process of the method disclosed by the invention, the use of a precious metal catalyst, namely palladium on carbon is avoided, the cost of auxiliary materials and the recovery cost are greatly reduced, the reaction conditions in each step are mild, the violent heat release and deflation phenomena are avoided, and the safety in production is good.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and in particular relates to a method for synthesizing medroxyprogesterone. Background technique [0002] Medroxyprogesterone, Chinese alias medroxyprogesterone acetate, medroxyprogesterone acetate, medroxyprogesterone ester, oxymedroxyprogesterone acetate, medroxyprogesterone, etc., is an important hormone drug, mainly used for dysmenorrhea , functional amenorrhea, functional uterine bleeding, threatened abortion or habitual abortion, endometriosis, treatment of advanced breast cancer, endometrial adenocarcinoma and kidney cancer, etc. [0003] At this stage, most domestic companies adopt the classic synthetic route: 17α-hydroxyprogesterone acetate is used as raw material, etherified, McFarland reaction, hydrolyzed to generate 6-position methine, and then 6-position hydrogenation reaction to generate Medroxyprogesterone acetate. [0004] Its synthetic route is as foll...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J7/00
Inventor 史永平
Owner BAOJI KANGLE BIOTECH
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