Unlock instant, AI-driven research and patent intelligence for your innovation.

Preparation method of sertaconazole nitrate intermediate

A technology of sertaconazole nitrate and intermediates, which is applied in the field of preparation of sertaconazole nitrate intermediates, can solve the problems of ozone depletion, atmospheric destruction, carbon tetrachloride use restrictions, etc., and achieve the improvement of yield and purity, less toxic effect

Inactive Publication Date: 2021-11-16
HAINAN HAISHEN TONGZHOU PHARM CO LTD
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] As we all know, after carbon tetrachloride volatilizes, gas molecules will react with ozone under light to deplete ozone, make the ozone layer thinner, and destroy the entire atmosphere. Therefore, for the needs of environmental protection, in actual industrial production, tetrachloride The use of carbon dioxide is gradually limited

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of sertaconazole nitrate intermediate
  • Preparation method of sertaconazole nitrate intermediate
  • Preparation method of sertaconazole nitrate intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1 prepares 3-methyl-7-chlorobenzo [b] thiophene

[0031] (1) Preparation of o-chlorophenylthioacetone

[0032] Add 80kg of purified water into the reaction kettle, turn on the stirring, add 2.92kg of sodium hydroxide while stirring to make it completely dissolved, and obtain a 3.6wt% sodium hydroxide solution, then add 10.4kg of o-chlorothiophenol, and stir at room temperature for 30 minutes; stir Add 6.66kg of chloroacetone at the bottom, stir and react for 60min after the addition is complete, let stand after the reaction, and separate into water layer and oil layer. Then add 21.36kg ether to extract the aqueous layer, and wash with water 3 times. The ether layer was collected in separate layers, combined with the oil layer and then distilled under reduced pressure to recover the ether to obtain 12.14 kg of o-chlorophenylthioacetone.

[0033] (2) Preparation of 3-methyl-7-chlorobenzo[b]thiophene

[0034] Add 121.4kg of polyphosphoric acid in reactor A, s...

Embodiment 2

[0035] The investigation of embodiment 2 bromination reaction solvent

[0036] With the 3-methyl-7-chlorobenzo[b]thiophene prepared in Example 1 as the substrate, N-bromosuccinimide (NBS) as the bromination reagent, and benzoyl peroxide as the initiator Agent, according to the following preparation process, investigate the preparation situation of 3-bromomethyl-7-chlorobenzo[b]thiophene when different kinds of organic solvents are used as reaction solvents.

[0037] Concrete preparation process is as follows:

[0038]

[0039] Add solvent and 3-methyl-7-chlorobenzo[b]thiophene to the reaction flask, irradiate with a 200W light bulb, add benzoyl peroxide under stirring, heat to boiling, add N-bromosuccinyl in batches imine, stirring was continued for 4 hours under boiling.

[0040] The feeding ratio of above-mentioned reaction is as follows:

[0041] raw material Feeding amount amount of substance The molar ratio of 3-Methyl-7-chlorobenzo[b]thiophene ...

Embodiment 3

[0052] Embodiment 3 solvent is cyclohexane

[0053] Add 228.54g of cyclohexane and 29.30g of 3-methyl-7-chlorobenzo[b]thiophene to the reaction flask, irradiate with a 200W light bulb, and under stirring, add 1.94g of benzoyl peroxide, heat to boiling, and batch Add 29.89 g of N-bromosuccinimide, and continue stirring for 5 hours under boiling. Cool, filter, concentrate the filtrate until there is precipitation, let it stand for 4 hours, filter, wash the filter cake with 21.8g of petroleum ether (II), and obtain 23.92g of yellow 3-bromomethyl-7-chlorobenzo[b]thiophene powder , its NMR spectrum is as figure 1 shown.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a preparation method of a sertaconazole nitrate intermediate, which comprises the following steps: by taking cyclohexane as a reaction solvent, reacting 3-methyl-7-chlorobenzo [b] thiophene with a bromination reagent in the presence of benzoyl peroxide to generate 3-bromomethyl-7-chlorobenzo [b] thiophene. According to the invention, cyclohexane is used as a reaction solvent for carrying a bromination reaction for preparing 3-bromomethyl-7-chlorobenzo [b] thiophene. Compared with carbon tetrachloride, cyclohexane has lower toxicity, and does not react with ozone to damage the atmosphere. Use is not limited, so that the industrial production is facilitated.

Description

technical field [0001] The invention relates to the technical field of preparation of pharmaceutical intermediates, in particular to a preparation method of a sertaconazole nitrate intermediate. Background technique [0002] Sertaconazole nitrate, molecular formula: C 20 h 15 Cl 3 N 2 OS·HNO 3 , chemical name 1-[2-(7-chlorobenzo[b]thiophen-3-yl)methoxy-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole nitrate, is artificial The synthetic imidazole broad-spectrum antifungal drug has inhibitory and killing effects on skin fungi, yeast, candida and aspergillus, and has strong antibacterial effect on gram-positive bacteria. [0003] The common synthesis process of sertaconazole nitrate is to make 1-(2,4-dichlorobenzene)-2-(1-imidazole)ethanol and 3-bromomethyl-7-chlorobenzo[b]thiophene into salt reaction to prepare sertaconazole nitrate. [0004] For the intermediate 3-bromomethyl-7-chlorobenzo[b]thiophene of sertaconazole nitrate, the patent document CN112694470A records the fol...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D333/54
CPCC07D333/54
Inventor 韦家华李博福刘玉
Owner HAINAN HAISHEN TONGZHOU PHARM CO LTD