Preparation method of doxycycline intermediate 11[alpha]-chloromethene oxytetracycline

The technology of chloromethicillin and chlorooxytetracycline is applied in the field of preparation of doxycycline intermediate 11α-chloromethicillin, which can solve the trouble of molecular sieve activation, the inability of molecular sieve to effectively activate and produce The process is cumbersome and other problems, to achieve the effect of reducing potential safety hazards, reducing environmental pressure, and high dehydration yield

Active Publication Date: 2020-07-03
SHANDONG GUOBANG PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In industrial production, the activation of molecular sieves is more troublesome for the requirements of the reaction itself. It is likely that the molecular sieves cannot be activated effectively, so the production process is complicated by loading and unloading molecular sieves or separating molecular sieves.

Method used

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  • Preparation method of doxycycline intermediate 11[alpha]-chloromethene oxytetracycline
  • Preparation method of doxycycline intermediate 11[alpha]-chloromethene oxytetracycline

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] The preparation method of 11α-chloromethoxytetracycline

[0028] Add 105.11g of dichloromethane into a 250ml reaction bottle equipped with a thermometer and mechanical stirring, cool the reaction bottle to -26°C, add 30.01g of 11α-oxytetracycline chloride, stir and disperse, and pour into Put 15.52 g of 1,1-dichloromethyl-N,N-dimethylamine into the reaction flask, keep warm at -20°C to -10°C and stir for 10 hours, and absorb the tail gas of feeding and reaction process with two-stage liquid caustic soda. After the reaction was completed, the detection conversion rate was 90.5%, and the selectivity was 97.6%. The yield is then 88.3%.

[0029] Wherein dehydrating agent (1,1-dichloromethyl-N,N-dimethylamine) preparation

[0030] Add 300.05g of dichloromethane and 100.02g of thionyl chloride into a 500ml reaction flask equipped with a thermometer and mechanical stirring, start stirring, cool the reaction flask to 3°C, and drop it into the reaction flask when it is sealed ...

Embodiment 2

[0032] The preparation method of 11α-chloromethoxytetracycline

[0033] Add 104.91g of dichloromethane into a 250ml reaction bottle equipped with a thermometer and mechanical stirring, cool the reaction bottle to -24°C, add 30.04g of 11α-oxytetracycline chloride, stir and disperse, and pour into 15.49 g of 1,1-dichloromethyl-N,N-dimethylamine (preparation method is the same as that in Example 1) was put into the reaction flask, kept at -20°C to -10°C and stirred for 13 hours. Feeding and reaction process tail gas is absorbed by two-stage liquid caustic soda. After the reaction was completed, the detection conversion rate was 93.5%, and the selectivity was 97.1%. The yield is then 90.8%.

Embodiment 3

[0035] The preparation method of 11α-chloromethoxytetracycline

[0036] Add 105.12 g of dichloromethane into a 250 ml reaction bottle equipped with a thermometer and mechanical stirring, cool the reaction bottle to -27°C, add 30.06 g of 11α-oxytetracycline chloride, stir and disperse, and pour into Put 23.29 g of 1,1-dichloromethyl-N,N-dimethylamine (the preparation method is the same as in Example 1) into the reaction bottle, keep warm at -20°C to -10°C and stir for 13 hours. Feeding and reaction process tail gas is absorbed by two-stage liquid caustic soda. After the reaction is finished, the detection conversion rate is 98.8%, the selectivity is 97.0%, and the yield is 95.8%.

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Abstract

The invention relates to the technical field of veterinary drugs, in particular to a preparation method of doxycycline intermediate 11[alpha]-chloromethene oxytetracycline. According to the preparation method, 11[alpha]-chloromethene oxytetracycline is taken as a raw material, dichloromethane is used as a solvent, and 1,1-dichloromethyl-N,N-dimethylamine is taken as a dehydrating agent to carry out reactions to obtain 11[alpha]-chloromethene oxytetracycline. By utilizing the preparation method, the production potential safety hazard can be reduced, the product yield is high, the generated waste salt is reduced, and the equipment type selection requirement is reduced.

Description

technical field [0001] The invention relates to the technical field of veterinary medicine, in particular to a preparation method of doxycycline intermediate 11α-chloromethycin. Background technique [0002] Doxycycline is an antibiotic drug, a tetracycline drug, that can treat chlamydia mycoplasma infection. It is mainly used for the treatment of respiratory, urinary tract and biliary tract infections caused by sensitive bacteria. Upper respiratory tract infection, tonsillitis, biliary tract infection, lymphadenitis, cellulitis, senile chronic bronchitis, etc. caused by sensitive gram-positive bacteria and gram-negative bacilli. Pneumonia, etc. It can still be used to treat cholera, and also to prevent falciparum malaria and leptospirosis infection. Therefore, this drug is widely used in veterinary medicine, and the market demand is very large. The preparation of doxycycline generally uses oxytetracycline as a raw material, which is dehydrated by chlorination and hydrog...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C231/12C07C237/26
CPCC07C231/12C07C2603/46C07C237/26Y02A50/30
Inventor 达先鹏李芳王伟宏曲俊腾李琦斌
Owner SHANDONG GUOBANG PHARMA
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