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Preparation process of benzofuran

A technology for benzofuran and preparation process, which is applied in the field of synthesis of pharmaceutical intermediates, can solve the problems of low ring-closing yield, difficulty in scale-up production, and high operating costs, and achieves the effects of short reaction time, easy purification, and simple operation.

Inactive Publication Date: 2012-09-05
GUANGDONG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Among the above-mentioned methods, method (1) is mainly used for preparing 2,3-disubstituted phenylpropanfuran. The main disadvantage is that the dehydration reaction often produces two kinds of ring-closing products, which are difficult to separate and have low yields, and the 2-haloketone raw material not easy to get
The main disadvantage of method (2) is that 2-(2'-hydroxyphenyl) ketone (being benzyl ketone) is difficult to prepare, and the acid-catalyzed dehydration ring-closing yield is very low
However, the disadvantage of this method is that it needs to be divided into three steps, and the operation cost is high.
[0005] 2-Alkylphenylpropanefuran is a popular structure in drug research and development. The existing synthetic methods have the disadvantages of using some expensive catalysts, low yield, high cost, and difficult to scale up the production process.
This route is currently the main production method used to prepare 2-methyl-6-methoxybenzofuran, and its disadvantages are low yield, high cost, and poor process controllability
[0008] Currently, there is no literature report on the preparation of benzofuran in a one-pot process using substituted salicylaldehyde or o-hydroxyphenyl alkanone and 2-halogen substituted carboxylic acid or carboxylate

Method used

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  • Preparation process of benzofuran
  • Preparation process of benzofuran
  • Preparation process of benzofuran

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1.2, the preparation of 3-dimethyl-6-methoxybenzofuran

[0044]

[0045] Add DMSO (80ml), 2-hydroxyl-4-methoxyacetophenone (5g, 0.03mol) in 250ml reaction bottle, add Cs at room temperature 2 CO 3 (25g, 0.077mol), and 2-chloropropionic acid (3.5g, 0.032mol) was added dropwise under stirring, and the dropping temperature was controlled below 60°C. After the dropwise addition, the temperature was raised to 100-120°C to react for 2 hours, the reaction was quenched by adding water, the pH was adjusted to 1 with hydrochloric acid, the product was extracted with organic solvent, washed with water, and purified by short column chromatography to obtain 4.9 g of the product with a yield of 92%. HNMR (ppm, CDCl 3 ): 7.33-7.35(d, 1H), 6.98-700(d, 1H), 6.83-6.85(d, 1H), 3.82(s, 3H), 2.11(s, 3H), 2.32(s, 3H).

Embodiment 2

[0046] The preparation of embodiment 2.2-methyl-6-methoxybenzofuran

[0047]

[0048] Add DMF (50ml) and 2-hydroxy-4-methoxybenzaldehyde (5g, 0.032mol) to a 250ml reaction flask, add NaH (2.4g, 0.1mol) at room temperature, and add 2-bromopropionic acid ethyl Ester (6g, 0.033mol), heated to 100-120°C for 2 hours, quenched with water, adjusted to pH=1 with hydrochloric acid, extracted with organic solvent, washed with water, and purified by column chromatography to obtain 4.95g of product with a yield of 95%. HNMR (ppm, CDCl 3 ): 7.28-7.30 (d, 1H), 6.94-6.95 (d, 1H), 6.78-6.81 (dd, 1H), 6.25 (s, 1H), 3.80 (s, 3H), 2.39 (s, 3H).

Embodiment 3

[0049] The preparation of embodiment 3.2-ethyl-3-methylbenzofuran

[0050]

[0051]Add NMP (80ml), 2-hydroxyacetophenone (5g, 0.037mol) in the 250ml reaction bottle, add K at room temperature 2 CO 3 (15g, 0.11mol), added dropwise ethyl 2-bromobutyrate (7.25g, 0.037mol) under stirring, raised the temperature to 100-120°C for 2 hours, quenched the reaction with water, adjusted the pH to 1 with hydrochloric acid, extracted, Washing with water and purification by column chromatography yielded 5.12 g, with a yield of 86%. HNMR (ppm, CDCl 3 ); 7.44-7.46 (m, 2H), 7.23-7.25 (m, 2H), 2.65 (q, 2H), 2.05 (s, 3H), 1.21 (t, 3H).

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Abstract

The invention relates to the field of medical intermediate synthesis, in particular to a process route for synthesizing an important medical intermediate benzofuran. The process route for synthesizing benzofuran mainly comprises the following step of: reacting substituted o-hydroxybenzaldehyde, o-hydroxyphenyl alkyl ketone, or o-hydroxybenzonitrile with 2-halogenated aliphatic acid or the corresponding ester under the action of alkali to obtain the corresponding substituted benzofuran. The invention provides a method for preparing benzofuran, which is simple and can realize industrialized production; and the process route provided by the invention has the characteristics of economy, rapidness, environmental friendliness, high yield and the like.

Description

technical field [0001] The invention relates to the field of synthesis of pharmaceutical intermediates, in particular, the invention relates to the synthesis of an important pharmaceutical intermediate, phenylpropanfuran. Background technique [0002] Phenylpropionfuran is an important pharmaceutical and chemical intermediate. It is the main structure of many natural products and drugs. It is the core structure of many medicines and many new drugs that are currently being developed. [0003] The synthetic method of the phenylpropanoid of bibliographical information can be divided into four kinds simply: (1) generate phenoxyalkanone with phenol and 2-halogenated ketone reaction, acid catalyzed direct dehydration and obtain phenylpropanoid product (Bull Soc Chem Jpn, 1971, 44, 749); (2) prepare 2-(2'-hydroxyphenyl) ketone first, and dehydrate under acidic conditions to obtain phenylpropanfuran (Tetrahedron Lett, 1980, 21, 4391); (3) use water Phenylaldehyde or 2-hydroxyphenyl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/79C07D307/82C07D307/80C07D307/85
Inventor 黄云生
Owner GUANGDONG MEDICAL UNIV
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