Preparation method of 7-hydroxy-1-indanone

Abstract

The invention relates to a novel synthetic method of 7-hydroxy-1-indanone (a compound IV). The technical problems that for an existing synthetic method, reaction conditions are harsher, by-products are more, after-treatment is difficult, and the raw materials are difficult to obtain are mainly solved. According to the preparation method of the 7-hydroxy-1-indanone, 4-hydroxy-benzenesulfonic acid (a compound I) is reacted with 3-chloropropionyl chloride to obtain a compound II, a reaction is conducted on the compound II on the condition that lewis acid exists to obtain a compound III, a sulfonic acid group of the compound III is removed, and the compound IV is obtained.

Description

technical field

[0001] The invention relates to a new preparation method of 7-hydroxyl-1-indanone. Background technique

[0002] 7-Hydroxy-1-indanone and related derivatives have a wide range of applications in medicinal chemistry and organic synthesis. The synthesis of this type of compound mainly contains the following three methods to synthesize 7-hydroxyl-1-indanone at present:

[0003] The first method is to use 3-(3-hydroxyphenyl) propionic acid as a raw material, in the presence of polyphosphoric acid, heat to 180 ° C (European Journal of Medicinal Chemistry, 2010, 25-37), and simultaneously obtain 7-hydroxy-1- Indanone and 5-hydroxyl-1-indanone are not easy to separate; the reaction requires high temperature heating and high energy consumption. The synthetic route of this method is as follows:

[0004]

[0005] The second method is to use 2,3-dihydrochromen-4-one as a raw material, add aluminum trichloride, and heat to 200°C (EP1426365; Tetrahedron Letters, 201...

Examples

Embodiment 1

[0019] (1) Preparation of compound II:

[0020]

[0021] Dissolve compound I, 4-hydroxybenzenesulfonic acid (34.8g, 0.2mol) in 500ml of acetonitrile, add triethylamine (0.2mol), cool to 0°C, add dropwise 3-chloropropionyl chloride (25.2g, 0.2mol) , stirred at 0°C for 0.5 hours, stirred at room temperature for 2 hours, and the reaction was detected by TLC spotting. The reaction liquid was washed with water, washed with 1M NaOH, washed with water, washed with saturated saline, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and concentrated under reduced pressure to obtain Compound II47.52g, yield 90%.

[0022] 1HNMR (400MHz, DMSO-d6): δppm7.81(dd,2H), 7.14(dd,2H), 3.68(t,2H), 2.39(t,2H); m / z=265(M+H)+ .

[0023] (2) Preparation of compound III:

[0024]

[0025] Compound II (42g, 0.159mol) was added to 450ml of dichloromethane, then tetraethyl titanate (108.7g, 0.477mol) was added, heated to 40°C, stirred for 16 hours, and detected by TLC, the re...

technical field

[0001] The invention relates to a new preparation method of 7-hydroxyl-1-indanone. Background technique

[0002] 7-Hydroxy-1-indanone and related derivatives have a wide range of applications in medicinal chemistry and organic synthesis. The synthesis of this type of compound mainly contains the following three methods to synthesize 7-hydroxyl-1-indanone at present:

[0003] The first method is to use 3-(3-hydroxyphenyl) propionic acid as a raw material, in the presence of polyphosphoric acid, heat to 180 ° C (European Journal of Medicinal Chemistry, 2010, 25-37), and simultaneously obtain 7-hydroxy-1- Indanone and 5-hydroxyl-1-indanone are not easy to separate; the reaction requires high temperature heating and high energy consumption. The synthetic route of this method is as follows:

[0004]

[0005] The second method is to use 2,3-dihydrochromen-4-one as a raw material, add aluminum trichloride, and heat to 200°C (EP1426365; Tetrahedron Letters, 201...

Examples

Embodiment 1

[0019] (1) Preparation of compound II:

[0020]

[0021] Dissolve compound I, 4-hydroxybenzenesulfonic acid (34.8g, 0.2mol) in 500ml of acetonitrile, add triethylamine (0.2mol), cool to 0°C, add dropwise 3-chloropropionyl chloride (25.2g, 0.2mol) , stirred at 0°C for 0.5 hours, stirred at room temperature for 2 hours, and the reaction was detected by TLC spotting. The reaction liquid was washed with water, washed with 1M NaOH, washed with water, washed with saturated saline, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and concentrated under reduced pressure to obtain Compound II47.52g, yield 90%.

[0022] 1HNMR (400MHz, DMSO-d6): δppm7.81(dd,2H), 7.14(dd,2H), 3.68(t,2H), 2.39(t,2H); m / z=265(M+H)+ .

[0023] (2) Preparation of compound III:

[0024]

[0025] Compound II (42g, 0.159mol) was added to 450ml of dichloromethane, then tetraethyl titanate (108.7g, 0.477mol) was added, heated to 40°C, stirred for 16 hours, and detected by TLC, the re...

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