Synthesis method of oxetanone

Abstract

The invention discloses a synthesis method of oxetanone. The method comprises the steps: in an organic solvent and in the presence of a catalyst, a halide and an alkali, utilizing an oxidant to oxidize oxetanol, and then separating and purifying to obtain oxetanone. The method adopts the organic oxidation system for oxidation production of oxetanone for the first time, is cheap in adopted materials and simple in operation, avoids use of methyl azide, butyl lithium, or 1,3-dichloroacetone and other dangerous chemicals, enables the synthesis method of oxetanone to be safely amplified, and can be produced in large scale; the method is friendly to the environment and avoids use of phosphorus pentoxide and other reagents, so that the process meets the requirements of environmental protection; and moreover, the method increases the reaction yield which is increased from 50% to 80% or more, thereby greatly reducing the production cost, and being in favor of further application and development of oxetanone in organic chemistry and biological medicines.

Description

technical field [0001] The present invention relates to a kind of synthetic method of oxetanone. Background technique [0002] In the research and development of small drug molecules, because certain positions of small drug molecules are easily biodegraded and lead to loss of activity, a disubstituted methyl group is usually introduced at these positions to avoid biodegradation of active small drug molecules. However, the introduction of a disubstituted methyl group will greatly increase the lipophilicity of the active drug molecule, which may make the small drug molecule more easily metabolized. Therefore, finding a more stable small group that does not change its lipophilicity to replace the disubstituted methyl group has become a very important and urgent goal in the development of small drug molecules. Eric Carreira et al found that the introduction of 3-oxetane on the small drug molecule can reduce its lipophilicity, increase its solubility, prevent the molecule from b...

AI Technical Summary

Problems solved by technology

Therefore, this method has great potential safety hazards and is not suitable for large-scale production.

[0017] The second method uses dangerous goods such as butyllithium and sodium hydrogen, which are flammable and explosive, which brings great safety hazards in production and is not suitable for production scale-up

Especially butyllithium needs to use ultra-low temperature conditions, which greatly increases the production cost

[0018] The third method uses 1,3-dichloroacetone as the starting material. Although the total yield reaches 50%, 1,3-dichloroacetone is a highly toxic drug, and it is very risky to purchase and use, so it is not suitable Amplified production; and when deprotecting with HCl in the second step, because oxetanone is unstable under acidic conditions, resulting in unstable yield, it is not suitable for enlarged production

[0019] The disadvantage of method four is that the yield is low, and phosphorus pentoxide or pyridinium chlorochromate which pollutes the environment is used, and the cost of waste treatment is high, which is not conducive to environmental protection

[0020] Although these methods can all produce 3-oxetanone, there are unavoidable potential safety hazards in the enlarged production, or can not meet environmental protection requirements, so that there are very few manufacturers producing 3-oxetanone, and its price Extremely expensive, which seriously hinders its further application and development in organic chemistry and biomedicine

Images