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Method for synthesizing acecloguanosine lateral chain

A technology of diacetoxy and oxetane, applied in 1 field, can solve the problems of complex environmental protection treatment process, influence normal production process, cannot be directly discharged, etc., and achieves cheap raw materials, high product yield, and fast reaction speed. Effect

Active Publication Date: 2013-06-05
ZHEJIANG CHARIOTEER PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But because this reaction needs to be through high-vacuum decompression distillation in aftertreatment process, catalyst itself has considerable solubility in product crude product and is brought into rectification tower, remains in the reboiler at the bottom of still during rectification process and can be separated out, carbonization is serious and Affect the normal production process
[0007] 3. The post-treatment of the anhydrous zinc chloride catalytic process is complicated. Usually, the salt is washed away with water, and some products dissolved in water are extracted with organic solvents. The sewage cannot be discharged directly because of zinc ions. The environmental protection treatment process is extremely complicated and the cost is too high. high
However, the existing published documents do not relate to the target product of the present invention and the ring-opening O-acylation reaction

Method used

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  • Method for synthesizing acecloguanosine lateral chain
  • Method for synthesizing acecloguanosine lateral chain
  • Method for synthesizing acecloguanosine lateral chain

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Mix 20g of phosphorus pentoxide and 15g of 85% analytically pure phosphoric acid reagent, heat to 80°C, continue to stir for 1 hour after completely dissolving, and cool slowly to obtain polyphosphoric acid, its P 2 o 5 The content is 83.5%, and the corresponding phosphorus polymerization degree is 4.

[0035] Add 0.5g of polyphosphoric acid and 100g of acetic anhydride prepared by the above method to a three-neck flask equipped with a reflux condenser, dropping funnel, thermometer and mechanical stirring, and raise the temperature to 60°C to completely dissolve the polyphosphoric acid in the acetic anhydride , the solution turned pale yellow. Cool the liquid in the reaction bottle to room temperature, then slowly add 67.5g of 1,3-dioxane dropwise, and control the rate of addition so that the temperature in the reaction bottle does not exceed 80°C. After the dropwise addition, keep the temperature at 45-50°C4 Hours, track and detect with gas chromatography, until the ...

Embodiment 2

[0037] Other operations are the same as in Example 1, but there are differences in the following aspects: the prepared polyphosphoric acid content is 85%, the polyphosphoric acid added by the reaction is 0.1g, acetic anhydride is 100g, and the anhydrous sodium acetate of 1.48g is changed into 1.30 g of anhydrous sodium carbonate, other reaction conditions and operations are the same as in Example 1, and 144.0 g of 1,4-diacetoxy-2-oxetane pure product is obtained, the purity is 98%, and the yield is 1,3 -Dioxane is calculated as 90%.

Embodiment 3

[0039] The operation is the same as in Example 1, but there are differences in the following aspects: after the addition, the reaction temperature of acetic anhydride and 1,3-dioxane is always controlled at 0-5° C., and the reaction time is 10 hours. 149.0 g of pure 1,4-diacetoxy-2-oxetane was obtained with a purity of 98.5% and a yield of 93% based on 1,3-dioxane.

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Abstract

The invention discloses a method for synthesizing an acecloguanosine lateral chain, which comprises the following steps: stirring 1,3-dioxolane and acetic anhydride at the temperature of between 0 and 100 DEG C for reaction in the presence of a catalyst of polyphosphoric acid or polyphosphoric acid organic ester derivatives, and tracing and detecting until the reaction is finished; adjusting a pHvalue with alkali, stirring uniformly, and filtering; distilling filter liquor under reduced pressure to remove non-reacted reactants and byproducts; and rectifying to obtain the refined product of acecloguanosine lateral chain. The method has the advantages that: the high-selectivity catalyst is used, the content of the crude acecloguanosine lateral chain is improved to 85 percent, the final yield of the product is improved, the operation of subsequent rectification is easier, the production cost is greatly reduced, and the production efficiency is improved.

Description

technical field [0001] The present invention relates to a pharmaceutical intermediate, in particular to an intermediate used in antiviral drugs acyclovir and valacyclovir hydrochloride series - 1,4-diacetoxy-2-oxetane synthetic method. Background technique [0002] [0003] Acyclovir (shown in formula 1) and valacyclovir hydrochloride (shown in formula 2) are antiviral drugs that replace guanines, and are widely used because they can effectively treat herpes and the like. Among them, valacyclovir hydrochloride can be automatically converted into acyclovir as a medicament in the human body. Literature Zou R, Robins MJ., Can.J.Chem.1987, 65:1436-1437; Literature Schaeff.HJ.DE.2539963, 1976.03.18; Literature Jerzy B, Bozenna G., Nucl. & Nucle.1989, 8(4): 529-536; Robins MJ., Haifield PW., Can. J. Chem. 1982, 60: 547-553 and Beauchamp LM, Doimatch BL, Schaeffer HJ, et al, J. Med. Chem ., 1985, 28:982-987 have reported the synthesis method of acyclovir. In these methods, t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C69/34C07C67/24B01J31/06
Inventor 蒲通陈海华王乃星李东兴范一陈云华陈恬潘彩丽
Owner ZHEJIANG CHARIOTEER PHARMA