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Preparation method of 5-penphene-2-formyl chloride

A technology of chlorothiophene and formyl chloride, applied in the direction of organic chemistry, can solve the problems of severe irritation to the eyes, skin and respiratory tract, high toxicity and corrosion, etc., achieve great implementation value and social economic value, less impurities, and short reaction cycle Effect

Inactive Publication Date: 2014-06-04
SHANGHAI INST OF PHARMA IND +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, oxalyl chloride is highly toxic and corrosive, and can severely irritate the eyes, skin and respiratory tract

Method used

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  • Preparation method of 5-penphene-2-formyl chloride
  • Preparation method of 5-penphene-2-formyl chloride
  • Preparation method of 5-penphene-2-formyl chloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1: Preparation of 5-chlorothiophene-2-formyl chloride

[0027] Add 14.5g (0.09mol) of 5-chlorothiophene-2-carboxylic acid into a 250ml four-necked bottle, add 150ml of dichloromethane and 12.5ml (0.09mol) of triethylamine to dissolve, connect the drying device and the acid gas absorption device. Dissolve 26.7g (0.09mol) of triphosgene in 50ml of dichloromethane (1.8mol / L), drop it into a four-necked flask at room temperature, and stir and reflux for 20 hours. After the reaction, an appropriate amount of anhydrous magnesium sulfate was added to the system, stirred, suction filtered, and the mother liquor was rotary evaporated to obtain 17 g of a yellow oil, and the yield of the crude product was 100%.

Embodiment 2

[0028] Embodiment 2: Preparation of 5-chlorothiophene-2-formyl chloride

[0029] Add 14.5g (0.09mol) of 5-chlorothiophene-2-carboxylic acid into a 250ml four-necked bottle, add 150ml of dichloromethane and 7.2g (0.09mol) of pyridine to dissolve, connect the drying device and the acid gas absorption device, at room temperature Put the dichloromethane solution of triphosgene (26.7g / 50ml=1.8mol / L) dropwise into the four-neck flask, stir and reflux for 20 hours. After the reaction, an appropriate amount of anhydrous sodium sulfate was added to the system, stirred, filtered with suction, and the mother liquor was rotary evaporated to obtain 17.5 g of a yellow oil, and the yield of the crude product was 100%.

Embodiment 3

[0030] Embodiment 3: Preparation of 5-chlorothiophene-2-formyl chloride

[0031] Add 8.1g (0.05mol) of 5-chlorothiophene-2-carboxylic acid in a 250ml four-necked bottle, add 100ml of dichloromethane and 5.5ml (0.04mol) of triethylamine to dissolve, connect the drying device and the acid gas absorption device, and At 40°C, drop triphosgene in dichloromethane (26.7g / 50ml=1.8mol / L) into a four-neck flask, stir and reflux for 8 hours. After the reaction, an appropriate amount of anhydrous magnesium sulfate was added to the system, stirred, suction filtered, and the mother liquor was rotary evaporated to obtain a yellow oil and an insoluble solid (raw material). GC detected that the reaction was incomplete, and the yield was 84%.

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Abstract

The invention relates to the technical field of a preparation method of 5-penphene-2-formyl chloride. The preparation method is characterized in that 5-penphene-2-carboxylic acid is taken as an initial raw material to react with chloro-reagent diphosgene or triphosgene in the presence of an organic amine catalyst, so as to prepare the 5-penphene-2-formyl chloride. The preparation method has the advantages that the process is simple, the production is safe and reliable, the reaction yield is high, the production cost is low, three wastes are not basically generated, a product is high in purity and has few impurities, and the preparation method is very suitable for industrial production. The 5-penphene-2-formyl chloride prepared by utilizing the preparation method is taken as an intermediate to prepare Rivaroxaban.

Description

technical field [0001] The invention relates to the technical field of a preparation method of 5-chlorothiophene-2-formyl chloride, a key intermediate of rivaroxaban. Background technique [0002] Rivaroxaban is an oxazolidinone compound with the chemical name 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)benzene Base]-1,3-oxazolidin-5-yl}-methyl)-2-thiophenecarboxamide, its structure is the following formula (I). Rivaroxaban is used as a direct inhibitor of coagulation factor Xa and may be used as a drug for the prophylaxis and / or treatment of thromboembolic disorders, especially in adult patients undergoing elective hip or knee replacement surgery, to prevent venous thrombosis ( VTE); for patients with non-valvular atrial fibrillation to reduce stroke and systemic embolism; for the treatment of acute coronary events, especially indeterminate angina. [0003] [0004] 5-Chlorothiophene-2-formyl chloride (Ⅲ) is the key intermediate for the synthesis of rivaroxaban. ...

Claims

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Application Information

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IPC IPC(8): C07D333/38
CPCC07D333/38
Inventor 王磊钟静芬韩强时惠麟
Owner SHANGHAI INST OF PHARMA IND
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