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Preparation method of cortisone acetate

A technology of cortisone acetate and glacial acetic acid, applied in the direction of steroids, organic chemistry, etc., can solve the problems of insufficient quality and yield, increased production cost, and many side reactions, so as to achieve good product quality and yield, save Production costs, effects of avoiding side effects

Active Publication Date: 2014-04-16
HENAN LIHUA PHARMA
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

After the 16α, 17α-epoxyprogesterone is oxidized to α-OH (11α-hydroxyl-16α, 17α-epoxyprogesterone) in Rhizopus niger at the C11 position, the α-OH on C11 is oxidized with chromic anhydride to a ketone group , followed by bromodebromination and iodine replacement to obtain cortisone acetate. The transformation process of the 21-position functional group in this reaction route: first, the halogenation reaction of carbonyl α-H, and then the replacement reaction to obtain the target product cortisone acetate. In China, expensive iodine is usually used as an auxiliary material, which greatly increases the production cost. At the same time, due to the existence of the 11-position carbonyl group, the selectivity in the process of adding iodine is poor, there are many side reactions, and the quality and yield are insufficient. Therefore, through the reaction Characterization of features and functional groups is of great significance to develop a new process with high efficiency and low energy consumption

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  • Preparation method of cortisone acetate
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  • Preparation method of cortisone acetate

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preparation example Construction

[0021] A preparation method of cortisone acetate, using 11α-hydroxyl-16α, 17α-epoxy progesterone as raw material, comprising the following steps:

[0022] (a) Upper bromine reaction:

[0023] Add 11α-hydroxyl-16α, 17α-epoxyprogesterone into hydrobromic acid, stir and react at 5~10°C for more than 5 hours, after the reaction is completed, add water for water analysis, filter, wash with water until neutral, and dry to obtain 11α, 17α-dihydroxy-16β-bromoprogesterone;

[0024] (b) debromination reaction:

[0025] Add 11α,17α-dihydroxy-16β-bromoprogesterone into ethanol and raise the temperature to 40-45°C and stir to dissolve, then add glacial acetic acid, active Raney nickel and pass hydrogen in sequence, keep the reaction for 3 hours, filter, concentrate and recover under reduced pressure solvent, filtered, washed with water until neutral, and dried to obtain 11α, 17α-dihydroxyprogesterone;

[0026] (c) Bromination reaction:

[0027] Add 11α, 17α-dihydroxyprogesterone into...

Embodiment 1

[0038] A preparation method of cortisone acetate, comprising the steps of:

[0039] (a) Bromine reaction: Preparation of 11α,17α-dihydroxy-16β-bromoprogesterone

[0040] Put 50g of 11α-hydroxyl-16α,17α-epoxyprogesterone and 150ml of hydrobromic acid into the reaction flask, stir and react at 5~10°C for 5 hours; after the reaction is completed, add 1000ml of water for water analysis, filter, and wash with water until neutral , drained, and dried to obtain 60 g of 11α, 17α-dihydroxy-16β-bromoprogesterone, with a TLC maximum point of 0.7%;

[0041] (b) Debromination reaction: Preparation of 11α,17α-dihydroxyprogesterone

[0042] Put 50g of 11α, 17α-dihydroxy-16β-bromoprogesterone and 1000ml of ethanol into the reaction bottle, heat up to 40-45℃ and stir to dissolve, then add 40ml of glacial acetic acid, 25g of Raney nickel in turn and pass hydrogen, keep the temperature for 3 hours , filtered, concentrated under reduced pressure to recover ethanol, filtered water to neutrality, s...

Embodiment 2

[0050] A preparation method of cortisone acetate, comprising the steps of:

[0051] (a) Bromine reaction: Preparation of 11α,17α-dihydroxy-16β-bromoprogesterone

[0052] Put 50g of 11α-hydroxyl-16α,17α-epoxyprogesterone and 150ml of hydrobromic acid into the reaction flask, stir and react at 5~10°C for 5 hours; after the reaction is completed, add 1000ml of water for water analysis, filter, and wash with water until neutral , drained, and dried to obtain 60 g of 11α, 17α-dihydroxy-16β-bromoprogesterone, with a TLC maximum point of 0.7%;

[0053] (b) Debromination reaction: Preparation of 11α,17α-dihydroxyprogesterone

[0054] Put 50g of 11α, 17α-dihydroxy-16β-bromoprogesterone and 1000ml of ethanol into the reaction bottle, heat up to 40-45℃ and stir to dissolve, then add 40ml of glacial acetic acid, 25g of Raney nickel in turn and pass hydrogen, keep the temperature for 3 hours , filtered, concentrated under reduced pressure to recover ethanol, filtered water to neutrality,...

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Abstract

The invention discloses a preparation method of cortisone acetate, and belongs to the field of pharmaceutical chemistry. According to the method, 11 alpha-hydroxy- 16 alpha, 17 alpha-epoxy progesterone is used as a raw material to prepare the cortisone acetate through bromine reaction, debromination reaction, bromination reaction, replacement reaction and oxidation reaction. The method can effectively avoid the occurrence of side reactions, and improves the quality of the product; at the same time, iodine is replaced by low-cost bromine for halogenating reaction, the production cost is greatly reduced, the method is high in efficiency and low in energy consumption, and the product quality and yield are good.

Description

technical field [0001] The invention relates to a preparation method of steroidal compounds in the field of drug synthesis, in particular to a preparation method of cortisone acetate, which belongs to the field of chemical pharmacy. Background technique [0002] Cortisone Acetate (Cortisone Acetate), also known as corticosterone acetate (Adreson), is a steroid hormone It is one of the varieties with the largest market demand in the class of raw materials, and it is also an important intermediate for the preparation of other high value-added steroid drugs. At present, Chinese, American and European pharmacopoeias are recorded. Its structural formula is: [0003] [0004] Cortisone acetate is a medium-acting adrenal cortex hormone drug, which acts on glucose metabolism and has a certain impact on electrolyte metabolism. It can reduce the pathological response of body tissues to damaging stimuli. It is used for severe bronchial asthma, severe dermatitis, etc. Allergic dis...

Claims

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Application Information

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IPC IPC(8): C07J5/00
Inventor 李合兴王海波李新安王泉泉
Owner HENAN LIHUA PHARMA
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