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Preparation method of 1-methyl-2,3-0-isopropylidene-5-deoxidized-D-ribofuranose

A technology of isopropylidene and ribofuranose, applied in the preparation of sugar derivatives, chemical instruments and methods, sugar derivatives, etc., can solve the problems of high cost, no advantage, low yield, etc., and achieve low cost and high product yield High, high-purity effect

Inactive Publication Date: 2013-08-07
ZHEJIANG SANHE PHARMACHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] As described in U.S. Patent US4340729, after 2,3-0-isopropylidene-1-0-methyl-D-ribose is brominated at the 5-position, it is hydrogenated and reduced with Pd / C to obtain 1-methyl-2, 3-0-isopropylidene-5-deoxy-D-ribofuranose, due to low yield, high cost has no advantage

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0013] Put into a 1000mL three-necked flask in turn 2-methyltetrahydrofuran (200.0g, 234 mL), 1-methyl-2,3-0-isopropylidene-5-0 p-toluenesulfonyl-D-ribofuranose (100.0g , 267mmol), potassium borohydride (18.7g, 347mmol), polyethylene glycol 400 (PEG400) (5.3g, 13mmol). Warm up to reflux reaction, TLC monitors the reaction to be complete, then cool to room temperature, add water (250mL) and stir, stand still and separate into layers. The organic layer is washed with water (100mL×2), dried sodium sulfate, filtered with suction, and the filtrate is recovered 2-formaldehyde 60.3g of crude tetrahydrofuran was obtained. The crude product was rectified at 55°C and 20mmHg to obtain the finished product. The finished product was analyzed by gas chromatography (GC) with a content of 99.8% 1-methyl-2,3-0-isopropylidene-5-deoxy. -D-ribofuranose (43.0g, yield 85.0%).

Embodiment 2

[0015] Put into a 1000mL three-necked flask in turn 2-methyltetrahydrofuran (250.0g, 293 mL), 1-methyl-2,3-0-isopropylidene-5-0 p-toluenesulfonyl-D-ribofuranose (100.0g , 267mmol), potassium borohydride (21.6g, 400mmol), PEG400 (10.7g, 27mmol). Warm up to reflux reaction, TLC monitors the reaction to be complete, then cool to room temperature, add water (250mL) and stir, stand still and separate into layers. The organic layer is washed with water (100mL×2), dried sodium sulfate, filtered with suction, and the filtrate is recovered 2-formaldehyde 62.0g of crude tetrahydrofuran was obtained. The crude product was rectified at 55°C and 20mmHg to obtain the finished product. The finished product was analyzed by gas chromatography (GC) with a content of 99.7% 1-methyl-2,3-0-isopropylidene-5-deoxy -D-ribofuranose (43.6g, yield 85.5%).

Embodiment 3

[0017] A 1000mL three-necked flask was sequentially put into 2-methyltetrahydrofuran (300.0g, 351mL), 1-methyl-2,3-0-isopropylidene-5-0 p-toluenesulfonyl-D-ribofuranose (100.0g, 267mmol), potassium borohydride (24.5g, 454mmol), PEG400 (16.0g, 40mmol). Warm up to reflux reaction, TLC monitors the reaction to be complete, then cool to room temperature, add water (250mL) and stir, stand still and separate into layers. The organic layer is washed with water (100mL×2), dried sodium sulfate, filtered with suction, and the filtrate is recovered 2-formaldehyde 64.1g of crude tetrahydrofuran was obtained. The crude product was rectified at 55°C and 20mmHg to obtain the finished product. The finished product was analyzed by gas chromatography (GC) with a content of 99.9% 1-methyl-2,3-0-isopropylidene-5-deoxy. -D-ribofuranose (44.1g, yield 86.5%).

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PUM

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Abstract

The invention discloses a preparation method of 1-methyl-2,3-0-isopropylidene-5-deoxidized-D-ribofuranose. The preparation method sequentially comprises the following steps of: dissolving 1-methyl-2,3-0-isopropylidene-5-O tosyl-D-ribofuranose into 2-methyltetrahydrofuran; adding potassium borohydride and polyethylene glycol 400; heating to perform a reflux reaction; monitoring complete reaction by thin-layer chromatography; cooling, adding water and layering; drying an organic layer by using anhydrous sodium sulphate; performing suction filtration; recovering a solvent from the filtrate to obtain a 1-methyl-2,3-0-isopropylidene-5-deoxidized-D-ribofuranose crude product; and rectifying the crude product under the conditions of 55 DEG C and 20 mmHg to obtain the finished product. The method is simple in reaction operation, high in product yield, high in purity, high in solvent recovery rate and easy in industrialization.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry and relates to a preparation method of capecitabine intermediate 1-methyl-2,3-0-isopropylidene-5-deoxy-D-ribofuranose. Background technique [0002] Capecitabine was developed by the Swiss pharmaceutical company Roche and was marketed in the United States, Canada, Sweden and other countries under the trade name Xeloda in 1998. At present, my country has approved the import of this product, which is clinically used in the treatment of advanced breast cancer, colorectal cancer and other solid tumors. Xeloda has less side effects, and general side effects often include fatigue, but severe cases are rare. Other common side effects were mucositis, fever, weakness, lethargy, etc., but none of them were serious. [0003] According to journals and patent literature reports, known synthesis such as structural formula ( ) of 1-methyl-2,3-0-isopropylidene-5-deoxy-D-ribofuranose as follows: ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H15/04C07H1/00
Inventor 金水东刘雄张立光洪家春杨卫东
Owner ZHEJIANG SANHE PHARMACHEM