Method for preparing etodolac methyl ester

A technology of methyl etodolac and methyl oxopentanoate, which is applied in the field of preparing indole non-steroidal anti-inflammatory analgesic etodolac, which can solve the problems of unsuitable industrialized production, many post-processing wastes, and high production costs. problems, to achieve the effect of low production cost, less three wastes and easy control

Active Publication Date: 2012-01-11
SHANDONG XINHUA PHARMA CO LTD
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

This process first prepares the isobutanol solution of hydrogen chloride, and the operation is complicated. After the reaction is completed, the mixture is directly poured into the aqueous sodium bicarbonate solution, the resulting product quality is poor, the yield is low, and there are many post-treatment wastes, and the production cost is high. In line with industrial production

Method used

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  • Method for preparing etodolac methyl ester
  • Method for preparing etodolac methyl ester

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Step A: Add 70.0 grams (content 79.3% W / W, 0.2935 moles) of 7-ethyl tryptophanol, 120 milliliters of anhydrous methanol, 360 milliliters of benzene and 45.8 grams of Methyl 3-oxopentanoate was cooled to 0~-5°C with stirring, and 86 g of concentrated sulfuric acid was added dropwise, and the mixture was kept at 0~-5°C and stirred for 1 hour.

[0017] Step B: After the reaction is completed, the layers are statically separated, the acid layer is separated, the acid phase is extracted once with toluene, the organic phases are combined, and neutralized with an aqueous solution of sodium carbonate. The organic phase was distilled to dryness under reduced pressure. Recrystallization with methanol gave 88 g (yield 99.55%) of methyl etodolac. Mp=129.5~131℃

Embodiment 2

[0019] Step A: Add 70.0 grams (content 79.3% W / W, 0.2935 moles) of 7-ethyl tryptophanol, 120 milliliters of anhydrous methanol, 480 milliliters of toluene and 45.8 grams of Methyl 3-oxopentanoate was cooled to 0~-5°C with stirring, and 86 g of concentrated sulfuric acid was added dropwise, and the mixture was kept at 0~-5°C and stirred for 1 hour.

[0020] Step B: Same as Step B of Example 1.

Embodiment 3

[0022] Step A: add 70.0 grams (content 79.3% W / W, 0.2935 mole) 7-ethyl tryptophanol, 120 milliliters of anhydrous methanol, 600 milliliters of dimethylbenzene and 45.8 milliliters in the 1000ml four-necked reaction flask that stirrer, thermometer are equipped with gram of 3-oxopentanoic acid methyl ester, stirred and lowered to 0~-5°C, added dropwise 86 grams of concentrated sulfuric acid, kept at 0~10°C and stirred for 1 hour.

[0023] Step B: Same as Step B of Example 1.

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Abstract

The present invention relates to a new process of preparing methyl etodolate as the intermediate of non-steroid indole anti-inflammatory analgesic etodolic acid. The process includes the reaction between 7-ethyl tryptosol and 3-methyl oxy valerate inside mixed solvent of C1-C2 alcohol and benzene in the presence of acid catalyst, separating out acid layer after reaction, neutralizing the organic phase, concentrating, re-crystallizing. The process has high stability, high yield, high product quality, conversion rate near to 100 %, simple operation low cost, environment friendship and other advantages, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a new process for preparing etodolac methyl ester, an intermediate of etodolac, which is an indole non-steroidal anti-inflammatory analgesic. Background technique [0002] Etodolac, whose chemical name is 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid (1,8-Diethyl-1 , 3,4,9-tetrahydropyrano[3,4-b]indol-1-acetic acid), for the treatment of rheumatoid arthritis, rheumatoid arthritis, osteoarthritis and postoperative pain, with strong analgesic effect. Methyl etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid methyl ester) is an important compound for the synthesis of etodolac Intermediate, which can generally be prepared from 7-ethyl tryptophanol and methyl 3-oxopentanoate (see US6,006,741) and its reaction is as follows: [0003] [0004] The original process is to add 20% hydrogen chloride isobutanol solution dropwise into toluene dissolved with 7-ethyl tryptophanol and methyl 3-oxop...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D491/052
Inventor 朱连博王冲
Owner SHANDONG XINHUA PHARMA CO LTD
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