Asymmetric synthesis method of 3-(3,4-dihydroxy phenyl)-2-hydracrylate

A technology of hydroxypropionate and dihydroxyphenyl is applied in the field of medicine and health to achieve the effect of high optical purity and easy operation

Active Publication Date: 2011-04-27
NORTHWEST UNIV(CN)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

This method can only synthesize racemic products

Method used

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  • Asymmetric synthesis method of 3-(3,4-dihydroxy phenyl)-2-hydracrylate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Synthesis of 3,4-dibenzyloxybenzaldehyde (1)

[0029] Dissolve 2.76g (20 mmol) of 3,4-dihydroxybenzaldehyde in 40 mL of anhydrous DMF, add 13.8 g of anhydrous potassium carbonate and 6.32 g (50 mmol) of benzyl chloride in sequence, and react the mixture at 75°C for 4 h. After filtering and concentrating the filtrate, the resulting oil was poured into 50 mL of distilled water with stirring, resulting in a large amount of solid, which was filtered and dried to obtain 5.78 g of a pale yellow solid, with a yield of 90.8%. m.p. 90°C-91°C.

Embodiment 2

[0030] Example 2 E -Synthesis of 3-(3,4-dibenzyloxyphenyl)acrylic acid (2)

[0031] Add 6.0 g (18.9 mmol) of 3,4-dibenzyloxybenzaldehyde and 5.88 g (57 mmol) of malonic acid into a three-necked flask, add 30 mL of 1,4-dioxane, and then add a catalytic amount of Pyridine and piperidine were reacted under reflux for 5h, TLC showed that the starting material disappeared, and cooled to room temperature. The reaction solution was poured into ice water, concentrated HCl was added, and a large amount of white solid was precipitated, which was filtered and washed with water. The crude product was recrystallized with 95% ethanol to obtain 5.7 g of white solid, with a yield of 85%. m.p. 201-202°C. 1 H NMR (500 MHz, CDCl 3 ) , δ 7.67-7.63(d, J =15.85Hz, 1H),7.46-7.43(m,4H),7.39-7.36(m,4H),7.33-7.30(m,2H),7.14-7.13(d, J =1.95Hz,1H),7.10-7.08(dd, J 1 =1.9Hz, J 2 =2.0Hz, 1H), 6.94-6.92 (d, J =8.35Hz, 1H),6.25-6.22(d, J =15.85Hz, 1H), 5.21-5.19 (d, J =10.6Hz, 4H); ...

Embodiment 3

[0032] Example 3 E -Synthesis of isopropyl 3-(3,4-dibenzyloxyphenyl)acrylate (3)

[0033] Will Z - 3.0 g (8.3 mmol) of 3-(3,4-dibenzyloxyphenyl) acrylic acid and 50 mL of isopropanol were added to the flask, and 1 mL of concentrated H 2 SO 4 , refluxed for 15h, TLC showed that the raw material disappeared, placed at room temperature, slowly added 50 mL saturated NaHCO 3 , extracted with toluene (3×30 mL), separated the organic layer, anhydrous MgSO 4 Dry, filter, and remove the solvent under reduced pressure to give a white solid. Recrystallized with ethyl acetate: n-hexane = 1:3 to obtain 2.7 g of the product with a yield of 80%. m.p.113.7℃-114.5℃. 1H NMR (400 MHz, CDCl 3 ) ,δ 7.59-7.55 (d, J =16Hz, 1H),7.49-7.45(m,5H),7.41-7.35(m,5H),7.14(s,1H),7.10-7.08(d, J =8.4Hz, 1H),6.95-6.93(d, J = 8.4Hz, 1H),6.27-6.23(d, J =15.6Hz, 1H), 5.22-5.20(d, J =8.8Hz, 4H),5.16-5.11 (m,1H), 1.33-1.32(d, J =6.4Hz, 6H); 13 C NMR (125 MHz, CDCl 3 ), δ for MS C. 22 26 h...

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Abstract

The invention discloses an asymmetric synthesis method of 3-(3,4-dihydroxy phenyl)-2-hydracrylate, which comprises the following concrete steps: reacting 3,4-dihydroxy benzene formaldehyde as a raw material with propandioic acid in a Knoevenagel condensation reaction mode under the protection of the phenolic hydroxyl group to obtain Z-3-(3,4-dibenzyloxyphenyl)acrylate, carrying out asymmetric dihydroxylation reaction to respectively obtain 3-(3,4-dibenzyloxyphenyl)-2,3-dihydroxyl propionate, and finally, carrying out catalytic hydrogenation to obtain the target product. The method provided bythe invention has the advantages of easy acquisition of raw materials and high optical purity of the product, is simple and convenient in operation, and is suitable for large-scale synthesis.

Description

technical field [0001] The invention relates to an asymmetric synthesis method of a chiral drug 3-(3,4-dihydroxyphenyl)-2-hydroxypropionate monorotor for preventing cardiovascular and cerebrovascular diseases, and belongs to the technical field of medicine and health. Background technique [0002] Cardiovascular and cerebrovascular diseases are one of the major diseases that endanger human life and health. Its fatality rate has surpassed that of tumors and has leapt to the first place, and drug treatment is the most important treatment method. Compound Danshen Dripping Pills, Guanxin Danshen Tablets and Danshen Drink are famous prescriptions for treating cardiovascular and cerebrovascular diseases. They have a long history of application in my country and have made important contributions to the treatment of cardiovascular and cerebrovascular diseases. The mechanism is not clear and so on. Since 1999, the inventor has carried out research on compound Danshen prescriptions su...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C69/732C07C67/327C07C67/31
Inventor 郑晓晖姜茹张群正王世祥陈明南叶飞
Owner NORTHWEST UNIV(CN)
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