Preparing process of 2-(10-oxy-10,11-dihydrodibenz [b,f]-thiotropilium-2-yl) propionic acid

A technology of phenylthiophenylacetate and thiazepine is applied in the field of preparation of zaltopprofen, can solve problems such as being unsuitable for industrialized production, long reaction steps, low total yield, etc., and achieves the advantages of being beneficial to industrialized production, Low cost and the effect of reducing the amount of iodine

Inactive Publication Date: 2007-06-27
常州市康瑞化工有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] This method requires the use of expensive potassium borohydride, highly polluting hydrobromic acid and highly poisonous potassium

Method used

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  • Preparing process of 2-(10-oxy-10,11-dihydrodibenz [b,f]-thiotropilium-2-yl) propionic acid
  • Preparing process of 2-(10-oxy-10,11-dihydrodibenz [b,f]-thiotropilium-2-yl) propionic acid
  • Preparing process of 2-(10-oxy-10,11-dihydrodibenz [b,f]-thiotropilium-2-yl) propionic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] 1, the preparation of methyl o-chlorophenylacetate (15)

[0113] Raw material (molecular weight)

Specification

Feeding amount

o-Chlorophenylacetic acid (170.5)

Industrial first-class product, white with acetic acid smell

color powder. MP95~97℃

10Kg

Methanol(32)

Colorless, transparent, flammable and volatile polar liquid

Body ≥ 99%

19Kg

Concentrated sulfuric acid (98)

Colorless transparent oily liquid, strong corrosion,

Content≥98%

1.14Kg

[0114] Feeding ratio (molar ratio):

[0115] O-chlorophenylacetic acid: methanol: concentrated sulfuric acid = 1: 10.12: 0.20

[0116] Add o-chlorophenylacetic acid and methanol to the reaction kettle respectively, stir, add concentrated sulfuric acid dropwise under cooling, heat up and reflux for 10 hours, and remove the solvent. Add water, separate layers, neutralize the organic layer, wash with water, dry, and distill to obtain 9.4Kg...

Embodiment 2

[0147] Embodiment 2: the preparation of 5-(1-carboxyethyl)-2-phenylthiophenylacetic acid (4) (without catalyst)

[0148] Raw material specification and feeding amount

[0149] Raw material (molecular weight)

Specification

Feeding amount

5-propionyl-2-phenylthio

Methyl phenylacetate (314)

White flaky crystal, content ≥

99%

4.84Kg

Iodine (256)

Purple-black scaly crystals, rotten

Corrosion, easy sublimation. industrial grade

≥98%

7.9Kg

Trimethyl orthoformate

(106)

Colorless liquid, ester fragrance

Taste, content ≥ 98%

23Kg

Potassium hydroxide (56)

strong alkaline white flake

GB1919-80 content 90%,

Deliquescence

3.9Kg

Chloroform solvent (for extraction)

water

tap water

30Kg

Sodium Thiosulfate(248)

Colorless transparent mono italic crystal

Body HG 1-210-79 content

≥98%

12Kg

[0150] Fe...

Embodiment 3

[0152] Embodiment 3: Preparation of 5-(1-carboxyethyl)-2-phenylthiophenylacetic acid (4) (without adding sodium thiosulfate)

[0153] Raw material specification and feeding amount

[0154] Raw material (molecular weight)

Specification

Feeding amount

5-propionyl-2-phenylthio

Methyl phenylacetate (314)

White flaky crystal, content ≥

99%

4.84Kg

[0155] Iodine (256)

Purple-black scaly crystals, rotten

Corrosion, easy sublimation. industrial grade

≥98%

3.95Kg

Trimethyl orthoformate

(106)

Colorless liquid, ester fragrance

Taste, content ≥ 98%

23Kg

Catalyst (Cuprous Chloride)

(99.5)

0.020Kg

Potassium hydroxide (56)

strong alkaline white flake

GB1919-80 content 90%,

Deliquescence

3.9Kg

Chloroform solvent (for extraction)

industrial grade

water

tap water

30Kg

[0156] Feed ratio (molar rati...

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PUM

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Abstract

The improved preparation process of zaltoprofen, named chemically as 2-(10-oxy-10, 11-dihydrodibenz [b, f]-thiotrppilium-2-yl) propionic acid, includes the following steps: rearrangement reaction of 5-propionyl-2-thiophenyl phenylacetate, iodine and triamyl orthoformate in the presence or absence of catalyst to obtain 5-(1-alkoxycarbonylethyl)-2-thiophenyl phenylacetate; hydrolyzing the said reaction product in water solution of alkali metal hydroxide and acidifying to obtain 5-(1-carboxylethyl)-2-thiophenyl phenylacetate; and the cyclization of 5-(1-carboxylethyl)-2-thiophenyl phenylacetate in the presence of polyphosphate to obtain the ultimate product. The present invention has low cost, less reaction steps, high yield, simple operation and no environmental pollution.

Description

technical field [0001] The present invention relates to a kind of preparation method of zaltoprofen, and its chemical name is 2-(10-oxo-10,11 dihydrodibenzo[b, f]thiepin-2-yl) propionic acid ( 1). Background technique [0002] Zaltoprofen is a potent non-steroidal anti-inflammatory, analgesic, and antipyretic drug. It acts selectively on the site of inflammation and has no effect on other organs such as stomach and kidney. Compared with similar drugs such as naproxen and ibuprofen, it has the characteristics of high efficiency and less gastric side effects. Its structural formula is as follows: [0003] [0004] There are many synthetic routes of Zaltoprofen, and the disclosed synthetic routes are listed as follows: [0005] One, take 5-propionyl-2-phenylthiophenylacetic acid methyl ester (2) as raw material to prepare zaltoprofen [0006] 1. Japanese Patent Application Laid-Open No. 61-251682 [0007] 5-(1-methoxycarbonylethyl)- 2-Phenylthiophenylacetic acid methy...

Claims

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Application Information

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IPC IPC(8): C07D337/14C07C319/14C07C321/30
Inventor 陈文华袁根林
Owner 常州市康瑞化工有限公司
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