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Preparation method of (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine and preparation intermediate of (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine

A technology for intermediates and ethylamines, applied in the field of preparing -1--ethylamine salts, can solve the problems of low yield, high price, complicated post-processing and the like

Pending Publication Date: 2022-05-27
HEBEI LANSHENG BIOTECH CO LTD +2
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  • Abstract
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  • Claims
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AI Technical Summary

Problems solved by technology

[0003] (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine is an important intermediate for the synthesis of benthiazil. The synthesis methods reported in the literature are: (1) 2-amino-5-fluoro Thiophenol and (R)-4-methylazolidine-2,5-dione were produced by simple thiazole ring synthesis under acidic conditions, but the yield was low; (2) 2-amino-5- Fluorothiophenol and 1,1,1-trichloroacetone are reacted to obtain (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine through cyclization and reduction. The raw materials used in this method 1,1,1-Trichloroacetone is expensive, and the reduction is difficult to prepare (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine with high purity; (3)2-Amino-5 -Metal salt of fluorothiophenol and N-carbonyl-D-alanine anhydride are ring-closed under acidic conditions, this method needs nitrogen protection, reacts for a long time at low temperature, and the waste water that produces contains heavy metal ions is difficult to handle; ( 4) 2-amino-5-fluorothiophenol and Boc-D-alanine are prepared by cyclization and deprotection of amino groups. This method is complicated in post-treatment and low in yield

Method used

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  • Preparation method of (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine and preparation intermediate of (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine
  • Preparation method of (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine and preparation intermediate of (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine
  • Preparation method of (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine and preparation intermediate of (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine

Examples

Experimental program
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Effect test

Embodiment 1

[0045]Add 240g of toluene, 40g of D-alanine, 68g of phthalic anhydride and 1g of triethylamine into the reaction flask, heat and reflux to separate water, react for 2.5-3.5h, add 66g of thionyl chloride dropwise, and control the dropping rate to Keep the temperature in the reaction bottle at 60-65°C. After dropping, raise the temperature to 77°C. After reacting for 5 hours, monitor and confirm the completion of the reaction by thin-layer chromatography, then concentrate at -0.06MPa and 55°C for 2 hours to obtain the formula (III) 106 g of the indicated acid chloride compound.

[0046] Under nitrogen protection, 43g of 2-amino-5-fluorothiophenol was dissolved in 128g of water, and the aqueous solution was added dropwise to 510g of hydrochloric acid with a concentration of 36wt%. After completion, 106 g of the acid chloride compound represented by the formula (III) prepared above was added dropwise, and the rate of addition was controlled so that the temperature was controlled a...

Embodiment 2

[0057] Add 635g of toluene, 61.5g of D-alanine, 102g of phthalic anhydride and 1g of triethylamine into the reaction flask, heat and reflux to separate water, react for 2.5-3.5h, add 82g of thionyl chloride dropwise, and control the dropping rate To keep the temperature in the reaction bottle at 60-65°C, after dropping, raise the temperature to 72°C, react for 5 hours, monitor and confirm the completion of the reaction by thin-layer chromatography, concentrate at -0.09MPa, 60°C for 1 hour, and obtain the formula (III) 164 g of the indicated acid chloride compound.

[0058] Under the protection of nitrogen, 43g of 2-amino-5-fluorothiophenol was dissolved in 85g of water, and the solution was added dropwise to 310g of hydrochloric acid with a concentration of 35wt%, and the dropping rate was controlled so that the temperature was always controlled at 0-10°C. After dropping, add 164 g of the acid chloride compound represented by the above-mentioned formula (III) dropwise, control...

Embodiment 3

[0061] Put 80.0 g of the compound of formula (I) into the reaction flask, add 1276 g of methanol aqueous solution with a concentration of 55 wt %, and 55 g of hydrazine hydrate, and conduct hydrazinolysis reaction at 45-50 ° C for 2.5-3.5 h under the protection of nitrogen, and then add hydrochloric acid to adjust to The pH is acidic, stirred for 1 h, cooled to below 15°C and filtered after the reaction, added 115 g of p-toluenesulfonic acid solution with a concentration of 50 wt % to the filtrate, cooled to 3°C to crystallize for 1.5 h, filtered to obtain the compound of formula (IV) 71.0 g of p-toluenesulfonate salt of (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine.

[0062] Add the above-prepared (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine methanesulfonate to an equal mass of water, adjust the pH to 10-12 with sodium hydroxide to dissolve the target compound , extract with dichloromethane, separate the layers, and concentrate the organic phase to obtain the compound of formu...

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Abstract

The present invention provides compounds represented by the following formula (I) or (II), and mixtures comprising both. The invention also relates to a preparation method for preparing (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine by using the compound shown in the formula (I) or (II) or a mixture containing the compound and the compound.

Description

technical field [0001] The present invention relates to a new method for preparing (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine salt and its intermediates. Background technique [0002] Amino acid pesticides refer to chemical products containing the basic structure of amino acids. These pesticides have the advantages of no acute toxicity to humans and animals, can be decomposed by microorganisms, and do not cause residual pollution. And the amino acid fatty acid produced after decomposition can improve the nutrition of the soil and the quality of agricultural products. In terms of fungicides, because of their safety to humans and the environment, they are currently one of the research hotspots of the world's pesticide companies. Benthiopyram is a class of high-efficiency small molecule peptide fungicides. Its application has been recognized by many countries and has broad application prospects. [0003] (R)-1-(6-fluoro-2-benzothiazolyl)-ethylamine is an important intermedi...

Claims

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Application Information

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IPC IPC(8): C07D417/06C07D209/48C07D277/64
CPCC07D417/06C07D209/48C07D277/64Y02P20/55
Inventor 郭红永郭庆春崔德保赵晓东张新刘伟伟李玉华王海臣
Owner HEBEI LANSHENG BIOTECH CO LTD
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