Preparation method of diphenylethane compound

A technology for diphenylethane and compounds, which is applied in the field of preparation of diphenylethane compounds, can solve the problems of heavy metal residues, harsh reaction conditions and the like, and achieves the effects of low synthesis cost, good stability and mild reaction conditions

Pending Publication Date: 2021-03-16
SHANGHAI INST OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The synthesis literature of erianin mostly uses the Wittig reaction to synthesize olefins first, and then prepares them by reducing the double bond with Pd / C. The Wittig reaction is a very efficient method for preparing olefins, but the reaction conditions are relatively harsh. The ylide reagent is sensitive to water and oxygen, and the aldehyde raw material The phenolic hydroxyl group is usually protected by a benzyl group, and an inert gas protection is required during the reaction, and water and air must be isolated during the synthesis process. In addition, the use of palladium carbon to dehydrogenate the benzyl group may cause heavy metal residues

Method used

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  • Preparation method of diphenylethane compound
  • Preparation method of diphenylethane compound
  • Preparation method of diphenylethane compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Preparation of (E) -3- (3-hydroxy-4-methoxyphenyl) -2- (3,4,5-trimethoxyphenyl) acrylic acid (3a):

[0033] 3,4,5-trimethoxyethylene acetic acid (50.0 g) and 3-hydroxy-4-methoxyceraldehyde (33.6 g) were placed in a 500 ml round bottom flask, and 200 ml of acetic anhydride was added, stirred and dissolved. 33.5 g of triethylamine was added, and the temperature was warmed to 100 ° C for 6-8 h. After the TLC point plate react was complete, cooled to room temperature, poured into ice water, and adjusted the pH of 1-2 with 1 M hydrochloric acid, stirred for 4 h, orange yellow solid, and filtered. The filter cake was dissolved in a 10% NaOH aqueous solution, extracted 3 times (discarded) with ethyl acetate, and the aqueous phase was adjusted to be 1-2 of 1-2, precipitated, washed with light yellow solid, filtrate, wash, dry, 62.5 g of light yellow solid, yield is 78.5%. 1 HNMR (500MHz, DMSO-D 6 Δ7.56 (S, 1H), 6.78 (D, J = 5.0 Hz, 1H), 6.60-6.56 (m, 2H), 6.44 (S, 2H), 3.72 (D, J =...

Embodiment 2

[0035] Preparation of (E) -3- (3-hydroxy-4-ethoxyphenyl) -2- (3,4,5-trimethoxyphenyl) acrylic acid (3b):

[0036] 3,4,5-trimethoxycetic acid (50.0 g) and 3-hydroxy-4-ethoxybenate (36.7 g) were placed in a 500 ml round bottom flask, 200 ml of acetic anhydride, stirred and dissolved, and then drop 57.1 g of diisopropyl ethyl amine was added, and the reaction was 10 ° C for 6-8 h. After the TLC point plate is complete, cool to room temperature. The reaction solution was poured into ice water, and the pH of 1-2 was adjusted with 1 M hydrochloric acid, precipitated orange yellow solid, and filtered. The filter cake was dissolved in a 10% NaOH aqueous solution, extracted 3 times with ethyl acetate, discarded the organic phase, the aqueous phase was 1 M hydrochloride pH of 1-2, precipitated light yellow solid, filtered, wash, dry 73.4G Yellow solid, yield is 88.8%. 1 H NMR (500MHz, CDCL 3 Δ7.66 (S, 1H), 7.32 (S, 1H), 7.03 (S, 1H), 6.87 (S, 1H), 6.87 (D, J = 10.0 Hz, 2H), 4.10 (Q, J = 5.0...

Embodiment 3

[0038]Synthesis of 2- (3-hydroxy-4-methoxyphenyl) -1- (3,4,5-trimethoxyphenyl) et-1-ketone (5a):

[0039] 50.0 g of Example 1 was placed in a 500 ml round bottom flask, and a stirrer was added, 200 mL of tert-butanol, triethylamine (14.9 g) and azide phosphate diphenyl ester (40.4 g) were added, stirred evenly, warmed Reaction reaction 15-18h. After the TLC point plate is complete, it is cooled to room temperature, stirred for 10 min, dissection, water washing, and the organic phase is subjected to rotation and recover tert-butanol.

[0040] The residue was dissolved in ethanol, and 6M hydrochloric acid was added, stirred for 1 h, solid precipitation, filtration, methanol water (1 / 1) washing, dried, 43.5 g of solid, yield of 94.0%. 1 H NMR (500MHz, CDCL 3 Δ7.62-7.59 (m, 2H), 6.90 (D, J = 10.0 Hz, 2H), 6.47 (S, 2H), 4.16 (S, 3H), 3.84 (S, 3H), 3.84 (S, 6H) ), 3.82 (s, 3h). 13 C NMR (125MHz, CDCL 3 ) Δ197.16,153.47,153.47,149.27,148.77,143.06,137.76,132.18,128.91,128.91,128.21,127.9...

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Abstract

The invention relates to a preparation method of a diphenylethane compound. The preparation method comprises the following steps: (1) dissolving 3,4,5-trimethoxyphenylacetic acid and 3-hydroxy-4-alkoxy benzaldehyde in an organic solvent, adding an organic alkali, and carrying out the Perkin reaction to obtain a stilbene acid intermediate; (2) dissolving the stilbene acid intermediate in an organicsolvent, adding diphenyl azide phosphate and organic alkali, and carrying out the Curtis rearrangement reaction to obtain an N-tert-butoxyacyl stilbene amine intermediate; (3) carrying out deprotection and hydrolysis on the N-tert-butoxyacyl stilbene amine intermediate by using strong acid to prepare a ketone intermediate; and (4) dissolving the ketone intermediate in an organic solvent, adding hydrazine hydrate and potassium hydroxide, and carrying out the Wolff-Kishner-Huang Minglong reduction reaction to prepare the diphenylethane compound having a structure as shown in a formula in the specification. In the formula, R is a methyl or an ethyl group. Compared with the prior art, the method of the invention has the advantages of mild reaction conditions, low synthesis difficulty, simplepost-treatment, mild storage conditions, safe synthesis process and the like.

Description

Technical field [0001] The present invention relates to the field of pharmaceutical techniques, and more particularly to a method of preparation of a dipyrene compound. Background technique [0002] Mae lacell, chemically called 3,4,5-trimethoxy-3'-hydroxy-4'-methoxy dihane (code: MLS) is a naturally available from the precious Chinese herbal medicine Diphenylthylene active ingredient with anti-tumor effect. Mulans has a common structural feature of the structatin A-4 (CA4, also known "CombretastatAn A-4 (CA4, also known as the wind), with a common AB ring structure, which is equivalent to the vinyl bridge. CA4. Like CA4, Mulan is also a microtubule inhibitor and has a strong tumor vascular target breaking effect, acting on the autumn water fairy base binding site. In addition, it is also possible to report that the anti-tumor effect of Mulanin is also possible to induce tumor cell apoptosis by acting in inhibiting VEGF expression, telomerase, liver cancer, melanoma, non-small ce...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C41/18C07C43/23C07C45/42C07C49/84C07C269/00C07C271/16C07C51/367C07C51/353C07C59/64
CPCC07C41/18C07C45/42C07C269/00C07C51/367C07C51/353
Inventor 吴范宏李玉洁黄金文刘运立夏郅聂辉李中原唐慧
Owner SHANGHAI INST OF TECH
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