Preparation method of 6,6-dimethyl-3-oxadicyclo[3.1.0]hexane-2,4-diketone

Abstract

The invention provides a preparation method of 6,6-dimethyl-3-oxadicyclo[3.1.0]hexane-2,4-diketone. The method comprises the following steps of: oxidizing first ethyl chrysanthemate serving as a raw material in water serving as a solvent by adopting potassium permanganate and adding sulfuric acid for hydrolyzing to generate 3,3-dimethyl-1,2-cyclopropane dicarboxylic acid; and performing cyclization on the 3,3-dimethyl-1,2-cyclopropane dicarboxylic acid in a system consisting of acetic anhydride and sodium acetate to generate the 6,6-dimethyl-3-oxadicyclo[3.1.0]hexane-2,4-diketone. The invention has the advantages that: water is taken as a reaction solvent, so that increase in cost and environmental pollution caused by the use of a large quantity of organic solvents are avoided; and a large amount of sulfur dioxide gas produced by the use of sodium metabisulfite is eliminated, so that environmental pollution and treatment of three wastes are greatly reduced. The method has the advantages of environmentally-friendly reaction process, low environmental pollution, simple process and low cost, thereby being beneficial to industrial production.

Description

technical field

[0001] The invention relates to the technical field of chemical industry, in particular to a preparation method of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione. Background technique

[0002] Hepatitis C is the leading cause of liver cirrhosis and liver cancer. New hepatitis C virus infections are increasing year by year, and it has become the leading reason for liver transplantation worldwide. The standard treatment for hepatitis C virus (pegylated interferon combined with ribavirin) is not satisfactory in terms of efficacy, and its side effects sometimes lead to discontinuation of treatment. With the in-depth understanding of the virus life cycle and protein structure, new drugs targeting the viral replication site have been developed, which can increase the sustained response rate by one-fold when used in combination with the current standard treatment regimen times.

[0003] 6,6-Dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione is an important intermediat...

Examples

Embodiment 1

[0020] Add 196Kg (1000mol) of the first ethyl chrysanthemum acid and 800Kg water to the 2000L reactor, start stirring, add 395Kg (2500mol) potassium permanganate in batches during the stirring process, add in 20 batches on average, control the reaction temperature when adding Between 30 and 50°C, after the addition, the mixture was reacted for 2 hours at 50 to 60°C, and then 1225 kg (10,000 mol) of sulfuric acid aqueous solution with a concentration of 80% was added to the reaction kettle. The temperature was raised to 70-80° C. for 12 hours. After the reaction, use circulating water to reduce the temperature in the kettle to 40-50°C, add 500L ethyl acetate to the kettle, and after stirring for 30 minutes, stop stirring, filter, and let the filtrate stand for stratification, and then use 500L ethyl acetate The ester was extracted once, and the organic phase was obtained by combining the two extractions. The ethyl acetate was evaporated under normal pressure, and then 300L petr...

Embodiment 2

[0023] Add 196Kg (1000mol) of the first ethyl chrysanthemum acid and 800Kg water to the 2000L reaction kettle, start stirring, add 790Kg (5000mol) potassium permanganate in batches during the stirring process, add in 40 batches on average, control the reaction temperature when adding Between 30 and 50°C, after the addition, the mixture was reacted at 50 to 60°C for 2 hours, and then 612.5Kg (5000mol) of sulfuric acid aqueous solution with a concentration of 80% was added to the reaction kettle. The internal temperature was raised to 70-80° C. for 12 hours. After the reaction, use circulating water to reduce the temperature in the kettle to 40-50°C, add 500L ethyl acetate to the kettle, and after stirring for 30 minutes, stop stirring, filter, and let the filtrate stand for stratification, and then use 500L ethyl acetate The ester was extracted once, and the organic phase was obtained by combining the two extractions. Ethyl acetate was evaporated under normal pressure, and 300L...

Embodiment 3

[0026] Add 196Kg (1000mol) ethyl chrysanthemum acid and 800Kg water to the 3000L reactor, start stirring, add 474Kg (3000mol) potassium permanganate in batches during the stirring process, add in 24 batches on average, control the reaction when adding The temperature is between 30-50°C. After the addition, the mixture is reacted at 50-60°C for 2 hours, and then 980kg (8000mol) of sulfuric acid aqueous solution with a concentration of 80% is added to the reaction kettle. After the addition, the kettle The internal temperature was raised to 70-80° C. for 12 hours. After the reaction, use circulating water to lower the temperature in the kettle to 40-50°C, add 500L ethyl acetate to the kettle, and after stirring for 30 minutes, stop stirring, filter, and let the filtrate stand for stratification, and then use 500L ethyl acetate The ester was extracted once, and the organic phase was obtained by combining the two extractions. The ethyl acetate was evaporated under normal pressure,...

technical field

[0001] The invention relates to the technical field of chemical industry, in particular to a preparation method of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione. Background technique

[0002] Hepatitis C is the leading cause of liver cirrhosis and liver cancer. New hepatitis C virus infections are increasing year by year, and it has become the leading reason for liver transplantation worldwide. The standard treatment for hepatitis C virus (pegylated interferon combined with ribavirin) is not satisfactory in terms of efficacy, and its side effects sometimes lead to discontinuation of treatment. With the in-depth understanding of the virus life cycle and protein structure, new drugs targeting the viral replication site have been developed, which can increase the sustained response rate by one-fold when used in combination with the current standard treatment regimen times.

[0003] 6,6-Dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione is an important intermediat...

Examples

Embodiment 1

[0020] Add 196Kg (1000mol) of the first ethyl chrysanthemum acid and 800Kg water to the 2000L reactor, start stirring, add 395Kg (2500mol) potassium permanganate in batches during the stirring process, add in 20 batches on average, control the reaction temperature when adding Between 30 and 50°C, after the addition, the mixture was reacted for 2 hours at 50 to 60°C, and then 1225 kg (10,000 mol) of sulfuric acid aqueous solution with a concentration of 80% was added to the reaction kettle. The temperature was raised to 70-80° C. for 12 hours. After the reaction, use circulating water to reduce the temperature in the kettle to 40-50°C, add 500L ethyl acetate to the kettle, and after stirring for 30 minutes, stop stirring, filter, and let the filtrate stand for stratification, and then use 500L ethyl acetate The ester was extracted once, and the organic phase was obtained by combining the two extractions. The ethyl acetate was evaporated under normal pressure, and then 300L petr...

Embodiment 2

[0023] Add 196Kg (1000mol) of the first ethyl chrysanthemum acid and 800Kg water to the 2000L reaction kettle, start stirring, add 790Kg (5000mol) potassium permanganate in batches during the stirring process, add in 40 batches on average, control the reaction temperature when adding Between 30 and 50°C, after the addition, the mixture was reacted at 50 to 60°C for 2 hours, and then 612.5Kg (5000mol) of sulfuric acid aqueous solution with a concentration of 80% was added to the reaction kettle. The internal temperature was raised to 70-80° C. for 12 hours. After the reaction, use circulating water to reduce the temperature in the kettle to 40-50°C, add 500L ethyl acetate to the kettle, and after stirring for 30 minutes, stop stirring, filter, and let the filtrate stand for stratification, and then use 500L ethyl acetate The ester was extracted once, and the organic phase was obtained by combining the two extractions. Ethyl acetate was evaporated under normal pressure, and 300L...

Embodiment 3

[0026] Add 196Kg (1000mol) ethyl chrysanthemum acid and 800Kg water to the 3000L reactor, start stirring, add 474Kg (3000mol) potassium permanganate in batches during the stirring process, add in 24 batches on average, control the reaction when adding The temperature is between 30-50°C. After the addition, the mixture is reacted at 50-60°C for 2 hours, and then 980kg (8000mol) of sulfuric acid aqueous solution with a concentration of 80% is added to the reaction kettle. After the addition, the kettle The internal temperature was raised to 70-80° C. for 12 hours. After the reaction, use circulating water to lower the temperature in the kettle to 40-50°C, add 500L ethyl acetate to the kettle, and after stirring for 30 minutes, stop stirring, filter, and let the filtrate stand for stratification, and then use 500L ethyl acetate The ester was extracted once, and the organic phase was obtained by combining the two extractions. The ethyl acetate was evaporated under normal pressure,...