Process for synthesizing 5-trifluoromethyl-1-indene ketone

A technology of trifluoromethyl and synthetic methods, applied in the field of new 5-trifluoromethyl-1-indanone synthesis, can solve the problems of harsh reaction conditions, long synthetic routes, expensive catalysts or raw materials, etc.

Active Publication Date: 2012-10-10
WUXI APPTEC (TIANJIN) CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Solve the technical problems existing in the current synthetic methods such as relatively long synthetic routes, expensive catalysts or raw materials, harsh reaction conditions, and high costs

Method used

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  • Process for synthesizing 5-trifluoromethyl-1-indene ketone
  • Process for synthesizing 5-trifluoromethyl-1-indene ketone
  • Process for synthesizing 5-trifluoromethyl-1-indene ketone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] 1. Synthesis of m-trifluoromethylcinnamic acid

[0023]

[0024] Add m-trifluoromethylbenzaldehyde (50 grams, 0.287mol), malonic acid (44.6 grams, 0.429mol), 15.4 milliliters of pyridine, and 0.72 milliliters of piperidine successively in a 500 milliliter three-neck flask equipped with a stirring bar, and start Stir and heat to 100°C for reflux reaction for 3-4 hours. Stop stirring, slowly pour into 300 ml of ice water while hot, slowly add 10% hydrochloric acid therein until the solid is completely precipitated, filter with suction, wash the solid with water, and dry in vacuo to obtain 60 g of a white solid product with a yield of 96.7%. It was directly used in the next reaction without purification. 2. Synthesis of m-trifluoromethylphenylpropionic acid

[0025]

[0026] Dissolve m-trifluoromethylcinnamic acid (58.6 grams, 0.27mol) in 600 milliliters of ethanol, add 10 grams of palladium hydroxide carbon (water content 50%), hydrogenate at room temperature (40 ...

Embodiment 2

[0031] Synthesis of 5-trifluoromethyl-1-indanone

[0032]

[0033] Add 48 ml of trifluoromethanesulfonic acid to a 250 ml three-necked flask, cool to -20°C, add m-trifluoromethylphenylpropionic acid (10 g, 45.87 mmol) dropwise under stirring, and react for 30 minutes and then naturally rise to room temperature , and stirred overnight at room temperature. Pour into ice water, extract three times with dichloromethane, wash with water, dry and concentrate under reduced pressure. Silica gel column chromatography separated 2.0 g of the product with a yield of 21.8%.

Embodiment 3

[0035] Synthesis of 5-trifluoromethyl-1-indanone

[0036]

[0037] Add 420 ml of trifluoromethanesulfonic acid into a 1000 ml three-necked flask, cool to -20°C, add m-trifluoromethylphenylpropionic acid (122 g, 0.56 mol) dropwise under stirring, and naturally rise to -10 mol after 30 minutes of reaction. ℃, stirred overnight at this temperature, poured into ice water, extracted three times with dichloromethane, washed with water, dried and concentrated under reduced pressure.

[0038] Silica gel column chromatography separated 16.7 g of the product with a yield of 14.9%.

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Abstract

The invention relates to a novel method for synthesizing 5-trifluoromethyl-1-indanone. The method comprises the following steps: adopting industrial m-trifluoromethyl benzaldehyde as raw material and preparing m-trifluoromethyl cinnamic acid by Knoevenagel condensation; hydrogenating to obtain m-trifluoromethyl phenylpropionic acid; and preparing 5-trifluoromethyl-1-indanone by intramolecular Friedel-Crafts acylation. The first step is carried out in the presence of malonic acid as organic reagent and pyridine or piperidine as catalyst under reflux at 100 DEG C. The second step is carried out in the presence of palladium / carbon or palladium hydroxide / carbon as catalyst and reaction solvent such as methanol, ethanol, ethyl acetate or tetrahydrofuran under a pressure of 40psi at room temperature. The third step is carried out with trifluoromethanesulfonic acid for closing rings at -20 DEG C-90 DEG C. The method provides a synthesis process for 5-trifluoromethyl-1-indanone which is simple and easy to be scaled, and solves the technical problems in prior art on relative long synthetic route, expensive catalyst or raw material, and severe reaction conditions, high cost, etc.

Description

Technical field: [0001] The present invention relates to a new method for synthesizing 5-trifluoromethyl-1-indanone. Background technique: [0002] 5-Trifluoromethyl-1-indanone and related derivatives are widely used in medicinal chemistry and organic synthesis. At present, the synthesis of such compounds mainly contains the following three methods: [0003] Method A is to use m-bromotrifluoromethylbenzene as a raw material, obtain an alkyne intermediate by Sonogashira coupling reaction, and then react under high temperature and high pressure under rhodium catalysis to obtain the corresponding product (Takeuchi, Ryo; Yasue, Hiroyuki; J.Org.Chem. 1993, 5386-5392). The disadvantage of this method is that precious metal catalysts are used in both steps, the raw materials are expensive, and large-scale production cannot be performed. [0004] The route of literature synthetic method A: [0005] [0006] The route of literature synthetic method B: [0007] Method B is to ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C49/477C07C45/46
Inventor 钟传富曹标张宗华高文忠马汝建陈曙辉李革
Owner WUXI APPTEC (TIANJIN) CO LTD
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