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Process for synthesizing 2-thiopheneethanol and derivatives thereof

A synthesis method, the technology of thiophene ethanol, which is applied in the field of medicine and chemical industry, can solve the problems of easy volatilization of bromine, many steps, cumbersome reaction, etc., and achieve the effect of reducing synthesis steps, mild reaction conditions, and avoiding formative reaction

Active Publication Date: 2013-03-13
ZHEJIANG LIAOYUAN PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the sodium reagent process, before the thiophene metal is sodiumized, the metal sodium needs to be divided into fragments, and then the metal sodium dispersion reagent is made in toluene, and then reacted with thiophene. This reaction is cumbersome, difficult to operate, and difficult for industrial production
In the ester reduction process, the process of preparing thiophene acetate requires operations such as thiophene acetylation, Willgerodt rearrangement, hydrolysis, and esterification. There are many steps, low yields of each part, low atom utilization, serious environmental pollution and sodium borohydride reduction. The agent is expensive and not suitable for industrial production
In the Grignard reagent process, there are disadvantages such as easy volatilization of bromine and serious corrosion to equipment.

Method used

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  • Process for synthesizing 2-thiopheneethanol and derivatives thereof
  • Process for synthesizing 2-thiopheneethanol and derivatives thereof
  • Process for synthesizing 2-thiopheneethanol and derivatives thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] (1) Preparation of the compound of formula 1: Under the protection of nitrogen, dissolve 33g of 2-bromothiophene, 48g of the compound of formula 4, 18g of sodium acetate, and 2.3g of palladium acetate in 200ml of N-methylpyrrolidone, stir and heat up to 135°C , kept warm for 9 hours, cooled to room temperature after the reaction, quenched by adding 200ml ice water, extracted 200mlⅹ2 with toluene, washed the organic phase with water 200mlⅹ2, then dried overnight with anhydrous sodium sulfate, filtered, and distilled under reduced pressure to obtain a viscous solid , adding 100ml of anhydrous methanol for recrystallization to obtain 48.7g of the compound of formula 1 as a white solid, with a yield of about 86%.

[0046] (2) Preparation of the compound of formula 2: In an organic solvent, 2.4 g of Pd / C (Pd mass fraction 10%) was added to 48.7 g of the compound of formula 1, and the 2 After replacing the air, the reaction pressure is 1-1.2MPa, and after stirring at 45-50°C ...

Embodiment 2

[0050] (1) Preparation of the compound of formula 1: Under the protection of nitrogen, dissolve 33g of 2-bromothiophene, 48g of the compound of formula 4, 18g of sodium acetate, and 2.3g of palladium acetate in 200ml of N-methylpyrrolidone, stir and heat up to 135°C , kept warm for 9 hours, cooled to room temperature after the reaction, quenched by adding 200ml ice water, extracted 200mlⅹ2 with toluene, washed the organic phase with water 200mlⅹ2, then dried overnight with anhydrous sodium sulfate, filtered, and distilled under reduced pressure to obtain a viscous solid , adding 100ml of anhydrous methanol for recrystallization to obtain 48.7g of the compound of formula 1 as a white solid, with a yield of about 86%.

[0051] (2) Preparation of the compound of formula 2: in an organic solvent, add 4.8 g of Pd / C (Pd mass fraction 10%) to 48.7 g of the compound of formula 1, and use H 2 After replacing the air, the reaction pressure was 1.0-1.2MPa, and after stirring at 45-50°C f...

Embodiment 3

[0055] (1) Preparation of compound of formula 1: Under nitrogen protection, dissolve 33g of 2-bromothiophene, 48g of compound of formula 4, 18g of sodium acetate, 4.6g of palladium acetate in 200ml of N-methylpyrrolidone, stir and heat up to 135°C , kept warm for 9 hours, cooled to room temperature after the reaction, quenched by adding 200ml ice water, extracted 200mlⅹ2 with toluene, washed the organic phase with water 200mlⅹ2, then dried overnight with anhydrous sodium sulfate, filtered, and distilled under reduced pressure to obtain a viscous solid , adding 100ml of anhydrous methanol for recrystallization to obtain 50.5g of the compound of formula 1 as a white solid, with a yield of about 89%.

[0056] (2) Preparation of the compound of formula 2: in an organic solvent, add 2.5 g of Pd / C (Pd mass fraction 10%) to 50.5 g of the compound of formula 1, and use H 2 After replacing the air, the reaction pressure was 1.0-1.2MPa, and after stirring at 45-50°C for 5 hours, the Pd / ...

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Abstract

The invention relates to a process for synthesizing 2-thiopheneethanol and derivatives thereof. 2-thiopheneethanol (formula 2) is synthesized by changing synthesis processes. The process is characterized by comprising the following steps: by taking 2-bromothiophene used as an initial material, carrying out Heck reaction to prepare the compound of formula 1; and then converting the compound of the formula 1 into 2-thiopheneethanol (formula 2) or the compound of formula 3 through selective reduction reaction. According to the process, 2-bromothiophene used as the initial material, Heck coupling reaction and reduction reaction are carried out to obtain 2-thiopheneethanol, and the cost is greatly reduced; the use of a catalytic amount of palladium avoids Grignard reaction, the reaction conditions are mild, the process is simple, and the pollution is small to be beneficial for industrial production as palladium is recovered; and the compound of the formula 1 can be converted into the compound of the formula 3 through the selective reduction reaction, and the compound of the formula 3 is a key intermediate in the process of synthesizing thiophene-2-ethylamine using 2-thiopheneethanol.

Description

technical field [0001] The invention belongs to the technical fields of medicine and chemical industry, in particular to a synthesis method of 2-thiophenethanol and its derivatives. Background technique [0002] 2-Thienyl ethanol and its derivatives are the raw materials for the synthesis of 2-thienyl ethylamine. 2-thienyl ethylamine can be used in the synthesis of various drugs, and it is the basis for the preparation of various new drugs for cardiovascular diseases and anti-inflammatory and analgesic related to platelets and thrombus. Key drug intermediates, such as ticlopidine hydrochloride, clopidogrel bisulfate and prasugrel hydrochloride, which are important drugs for the synthesis of cardiovascular and cerebrovascular diseases. With the continuous development of its downstream products, the prospect of 2-thiophenethanol and its derivatives will be even broader. [0003] There are many research reports on the synthesis process of 2-thiophene ethanol. The currently re...

Claims

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Application Information

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IPC IPC(8): C07D333/16C07D333/20
Inventor 胡华南屠雄飞林咸权陈双荣李浙东
Owner ZHEJIANG LIAOYUAN PHARM CO LTD
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