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Method for preparing (3S, 5S)-2, 3-dihydroxyl-5-hydroxymethyl tetrahydrofuran triacetate

A technology for hydroxymethyl tetrahydrofuran triacetate and dihydroxy is applied in the field of preparing (3R,5S)-2,3-dihydroxy-5-hydroxymethyl tetrahydrofuran triacetate, and can solve the problem of large solvent consumption, Difficult to industrialize, complex operation and other problems, to achieve the effect of simple operation, mild reaction conditions and simple process

Active Publication Date: 2012-11-28
SHANGHAI YINGLI PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The technical problem to be solved by the present invention is to overcome the existing synthetic (3S, 5S)-2,3-dihydroxyl-5-hydroxymethyltetrahydrofuran triacetate (formula B) method needs to adopt silica gel column separation product, The defects of large amount of solvent, complex operation, high cost and difficulty in industrialization provide a new method that is simple, feasible, low in cost and suitable for industrial production. This method can also achieve a higher yield

Method used

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  • Method for preparing (3S, 5S)-2, 3-dihydroxyl-5-hydroxymethyl tetrahydrofuran triacetate
  • Method for preparing (3S, 5S)-2, 3-dihydroxyl-5-hydroxymethyl tetrahydrofuran triacetate
  • Method for preparing (3S, 5S)-2, 3-dihydroxyl-5-hydroxymethyl tetrahydrofuran triacetate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Preparation of (3S, 5S)-2,3-dihydroxy-5-hydroxymethyltetrahydrofuran triacetate

[0047] Compound A (105 grams, 0.4mol), N, N-dimethyl-4-aminopyridine (5 grams, 0.04mol) were dissolved in acetic anhydride (400ml, 3.9mol), and concentrated sulfuric acid (mass concentration 98% , 10g, 0.1mol), the molar ratio of compound A to acetic anhydride and concentrated sulfuric acid is 1:10:0.25.

[0048] Under the protection of nitrogen, it was heated to 145° C. and reacted for 24 hours.

[0049] Cool to above 0°C and below 10°C, filter, and rinse the solid with cold ethyl acetate to obtain white solid C. The organic phases were combined, and the solvent was recovered by distillation under reduced pressure. The residue was rectified under reduced pressure, and the fraction of 1-2 mmHg and boiling point of 120-125° C. was collected to obtain 40 g of compound B with a yield of 39% and a purity of 95% by liquid chromatography (HPLC).

Embodiment 2

[0050] Example 2 Preparation of (3S, 5S)-2,3-dihydroxy-5-hydroxymethyltetrahydrofuran triacetate

[0051] Compound A (105 grams, 0.4mol), N, N-dimethyl-4-aminopyridine (5 grams, 0.04mol) were dissolved in acetic anhydride (300ml, 2.9mol), and acetic acid (300mL, 5.0mol) was added , the molar ratio of compound A to acetic anhydride and acetic acid is 1:7.2:12.5.

[0052] Under the protection of nitrogen, it was heated to 145° C. and reacted for 24 hours.

[0053] Cool to above 0°C and below 10°C, filter, and rinse the solid with cold ethyl acetate to obtain white solid C. The organic phases were combined, and the solvent was recovered by distillation under reduced pressure. The residue was rectified under reduced pressure to collect 1-2 mm Hg fractions with a boiling point of 120-125° C. to obtain 80 g of compound B with a yield of 78% and a purity of 95% by liquid chromatography (HPLC).

Embodiment 3

[0054] Example 3 Preparation of (3S, 5S)-2,3-dihydroxy-5-hydroxymethyltetrahydrofuran triacetate

[0055] Compound A (105 grams, 0.4mol), pyridine (5 grams, 0.06mol) are dissolved in acetic anhydride (300ml, 2.9mol), add acetic acid (300mL, 5.0mol), the molar ratio of A to acetic anhydride and acetic acid is 1:7.2:12.5.

[0056] Under the protection of nitrogen, it was heated to 145° C. and reacted for 24 hours.

[0057] Cool down to 80°C, recover acetic anhydride and acetic acid until dry. Cool to room temperature, add ethyl acetate, stir. Cool to above 0°C and below 10°C, filter, and rinse the solid with cold ethyl acetate to obtain white solid C. The organic phases were combined, and the solvent was recovered by distillation under reduced pressure. The residue was rectified under reduced pressure to obtain Compound B, 85 g, with a yield of 83%, and a purity of 94% by liquid chromatography (HPLC).

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Abstract

The invention discloses a synthesis method for preparing (3S, 5S)-2, 3-dihydroxyl-5-hydroxymethyl tetrahydrofuran triacetate which is shown in formula B. The method comprises the following step of: under the protection of inert gas, in polar organic solvent, leading compound A and acetylation reagent to have reaction under the action of protonic acid and / or lewis base; wherein Ac is acetyl. The method has simple operation, mild reaction condition and high yield, and the products B and C have industrial application valve and are in accordance with the green chemistry standard with atom economy. The subsequent products of the method are separated by the post-treatment methods such as filtering, rectification under vacuum and the like. Therefore, the method is simple and feasible, thus beingapplicable to not only laboratory small-scale preparation, but also large-scale industrialized production.

Description

technical field [0001] The invention relates to a novel organic synthesis method for preparing (3S, 5S)-2,3-dihydroxy-5-hydroxymethyltetrahydrofuran triacetate. Background technique [0002] (3S,5S)-2,3-Dihydroxy-5-hydroxymethyltetrahydrofuran triacetate has a structure as shown in Formula B: [0003] [0004] Wherein, Ac is acetyl. [0005] This compound is a derivative structure of sugar, which can be converted into the nucleoside drug parent. It is a commonly used intermediate in the field of drug synthesis, especially in the preparation of antibiotics for the treatment of bacterial infections, anti-AIDS drugs and diagnostic drugs for cancer. application. [0006] At present, the synthesis method of this compound needs to use silica gel column separation to obtain the product (Tetrahedron Vol.50.1994, pp.1435-1448; Journal of Organic Chemistry; 38; 1973; 3622-3623). Due to the disadvantages of high cost, complex operation and large amount of solvent used, so far, th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H13/06C07D473/34
Inventor 何成江王传旺李原强金仲恩
Owner SHANGHAI YINGLI PHARM CO LTD