Preparation method of 2-(4-bromomethyl)phenyl propionic acid

A technology of phenylpropionic acid and bromomethyl, which is applied in the field of preparation of 2-phenylpropionic acid, can solve the problem of high cost and achieve the effects of low toxicity, high purity and simple reaction

A technology of phenylpropionic acid and bromomethyl, which is applied in the field of preparation of 2-phenylpropionic acid, can solve the problem of high cost and achieve the effects of low toxicity, high purity and simple reaction

CN107501077AInactive Publication Date: 2017-12-22杭州乐敦科技有限公司 +1
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  • Preparation method of 2-(4-bromomethyl)phenyl propionic acid
  • Preparation method of 2-(4-bromomethyl)phenyl propionic acid
  • Preparation method of 2-(4-bromomethyl)phenyl propionic acid

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Experimental program
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Effect test

Embodiment 1

[0050]

[0051] Put 100g of compound 1 and 435g of concentrated hydrochloric acid into the reaction flask, under nitrogen protection, start stirring, raise the temperature to 65-70°C, and keep the reaction for 6 hours. TLC detection, after the reaction is complete, cool down to 20-30°C, stand still, separate the liquid, and collect the upper organic phase. The organic phase was washed with water for 3-4 times, dried over anhydrous sodium sulfate, and filtered to remove the desiccant to obtain light yellow liquid compound 2 with a yield of 123.5 g and a yield of 94.3%. directly used in the next reaction.

[0052] 1 H NMR (500MHz, CDCl 3 ): δ7.33(d, J=7.9Hz, 2H), 7.25(d, J=7.8Hz, 2H), 5.02(m, 1H), 2.36(s, 3H), 1.76(d, J=7.1Hz ,3H). MS: 155-156 (MH). HPLC: XDB-C18 4.6*250, methanol / water 1:1, 254nm, 45min.

Embodiment 2

[0054]

[0055] Put 60g of compound 1 and 260g of concentrated hydrochloric acid into the reaction bottle, protect it with nitrogen, start stirring, raise the temperature to 65-70°C, and keep it warm for 6 hours. TLC detection, after the reaction is complete, cool down to 20-30°C, stand still, separate the liquid, and collect the upper organic phase. The organic phase was washed with water for 3-4 times, dried over anhydrous sodium sulfate, and filtered to remove the desiccant to obtain light yellow liquid compound 2 with a yield of 73.8 g and a yield of 94%. directly used in the next reaction.

[0056] 1 H NMR (500MHz, CDCl 3 ): δ7.33(d, J=7.9Hz, 2H), 7.25(d, J=7.8Hz, 2H), 5.02(m, 1H), 2.36(s, 3H), 1.76(d, J=7.1Hz ,3H). MS: 155-156 (MH). HPLC: XDB-C18 4.6*250, methanol / water 1:1, 254nm, 45min.

Embodiment 3

[0058]

[0059] Put 70g of compound 1 and 600g of hydrobromic acid (40% content) into the reaction flask, protect it with nitrogen, start stirring, raise the temperature to 60-65°C, and keep the reaction for 5 hours. TLC detection, after the reaction is complete, cool down to 20-30°C, stand still, separate the liquid, and collect the upper organic phase. The organic phase was washed 3-4 times with water, dried over anhydrous sodium sulfate, and filtered to remove the desiccant to obtain light yellow liquid compound 3 with a yield of 108.5 g and a yield of 92%. directly used in the next reaction.

[0060] 1 H NMR (500MHz, CDCl 3 ): δ7.28 (m, 2H), 7.21 (m, 2H), 5.87 (m, 1H), 2.35 (s, 3H), 1.86 (d, J=7.8Hz, 3H). MS: 200-201 (MH).

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Abstract

The invention discloses a preparation method of 2-(4-bromomethyl)phenyl propionic acid. The preparation method includes the steps of: performing a reaction to a compound (I) (4-methylstyrene) with hydrogen halide to prepare a compound (II), performing a Grignard reaction and a carboxylation reaction to the compound (II) to obtain a compound (IV), and performing a bromination reaction to obtain a compound (V) (2-(4-bromomethyl)phenyl propionic acid), wherein a byproduct compound (VI) is subjected to a debromination reaction to obtain the compound (V) (2-(4-bromomethyl)phenyl propionic acid). The method is low in cost, has simple operations, is high in yield, is environment-friendly, and is suitable for industrial production.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis. Specifically, it relates to a preparation method of 2-(4-bromomethyl)phenylpropionic acid. Background technique [0002] 2-(4-bromomethyl)phenylpropanoic acid (2-(4-(bromomethyl)phenyl)propanoic acid), with a molecular weight of 243.1, is a key intermediate for the synthesis of loxoprofen sodium. Loxoprofen sodium was first developed by Japan's Sankyo Co., Ltd., and now it is the first-selling variety of non-steroidal anti-inflammatory drugs in Japan. It has been recorded by the Japanese Pharmacopoeia, and China has imported it. This product has been included in the National Ninth Five-Year Plan and one of the recommended trial varieties for new product development in 2010. [0003] The existing routes for synthesizing 2-(4-bromomethyl)phenylpropionic acid generally have the disadvantages of difficult sources of raw materials, complex production techniques, many by-products, and low ...

Claims

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Application Information

Patent Timeline
22 Dec 2017
Publication
CN107501077A
IPC
C07C51/377; C07C51/363; C07C57/58
CPC
C07C17/08; C07C51/15; C07C51/363; C07C51/377; C07F3/02; C07C57/58; C07C57/30; C07C22/04
Inventors
任峰波; 舒卫进