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Process method for synthesizing 2-substituted thiazole-4-boronic acid pinacol ester

A technology of pinacol ester and process method is applied in the field of preparing 2-substituted thiazole-4-boronic acid pinacol ester, and can solve the problem of high cost

Pending Publication Date: 2022-03-25
DALIAN NETCHEM CHIRAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The object of the invention is to solve the problem that the cost of synthesizing 2-substituted-thiazole-4-boric acid pinacol ester is unusually high at present, and a kind of process method of synthetic 2-substituted-thiazole-4-boric acid pinacol ester is provided, which is still Preparation of 2-substituted-thiazole-4-boronic acid pinacol esters by borylation reaction of metalorganic reagents with boric acid esters

Method used

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  • Process method for synthesizing 2-substituted thiazole-4-boronic acid pinacol ester
  • Process method for synthesizing 2-substituted thiazole-4-boronic acid pinacol ester
  • Process method for synthesizing 2-substituted thiazole-4-boronic acid pinacol ester

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Embodiment 1

[0021] A method for synthesizing a process method of 2-substituted thiazole-4-boronic acid pinacol ester, prepared according to the following steps,

[0022] Step 1, prepare 2-(trimethylsilyl)-4-bromothiazole:

[0023]

[0024] Weigh 150g of 2,4-dibromothiazole and dissolve it in 650mL of tetrahydrofuran, control the temperature at -10 to 0°C, add dropwise 264g of homemade 2.57mol / kg tetrahydrofuran solution of isopropylmagnesium chloride, after the dropwise addition, keep the reaction for 1h, The reaction of the raw materials is completely controlled in the gas phase, the temperature is controlled at -10 ~ 0°C, 73.8g of trimethylchlorosilane is added dropwise, after the drop is completed, the reaction is kept for 4 hours, the intermediate is controlled in the atmosphere, the intermediate is completely converted, the temperature is controlled at -10 ~ 0°C , drop into 50mL saturated brine to quench the reaction, stir the reaction for 10 minutes after the dropwise addition, f...

Embodiment 2

[0032] A method for the process of synthesizing 2-phenyl-thiazole-4-boronic acid pinacol ester, prepared according to the following steps,

[0033] Step 1, prepare 2-phenyl-4-bromothiazole:

[0034]

[0035] Weigh 200g of 2,4-dibromothiazole, 110.42g of phenylboronic acid, and 525.7g of potassium phosphate into a four-necked flask containing 2.2L of tetrahydrofuran, pass through nitrogen protection, add 11.96g of Xanyphos and 4.62g of Pd(OAc)2 , heated to 60 degrees to react for 8-14h, filtered, the filtrate was concentrated until no liquid dripped, and the chromatographic solution of ethyl acetate: n-heptane = 1:10 was passed through a silica gel column to obtain 134.5g of 2-phenyl-4-bromo Thiazole, GC purity 98.2%, yield 68%. [4]

[0036] Step 2, use trimethyl silicon to protect the 5-position carbon:

[0037]

[0038]Weigh 100g of 2-phenyl-4-bromothiazolyl in 410mL of tetrahydrofuran, control the temperature at -10 to 0°C, add dropwise 178g of homemade 2.57mol / kg t...

Embodiment 3

[0043] A method for the process of synthesizing 2-methoxythiazole-4-boronic acid pinacol ester, prepared according to the following steps,

[0044] Step 1, preparation of 2-substituted-4-bromothiazole:

[0045]

[0046] Weigh 250g of 2,4-dibromothiazole and dissolve it in 2.5L of methanol, add 166.8g of sodium methoxide and react at 20-30°C for 14-16h, concentrate under reduced pressure until no liquid drips, add 1.5L of methyl tert-butyl ether Extract with 1.5L of water, separate the liquids, extract the aqueous phase twice with 800mL methyl tert-butyl ether, combine the organic phases and concentrate under reduced pressure until no liquid drips, then purify by distillation under reduced pressure to obtain 149.8g of light yellow oil, GC purity 98.1%, yield 75.1%; [5]

[0047] Step 2, use trimethyl silicon to protect the 5-position carbon:

[0048]

[0049] Weigh 100g of 4-bromo-2-(methoxy)thiazolyl in 410mL of tetrahydrofuran, control the temperature at -10 to 0°C, ad...

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Abstract

The invention belongs to the field of organic chemistry, and relates to a method for preparing 2-substituted thiazole-4-boronic acid pinacol ester. The invention relates to a process method for synthesizing 2-substituted thiazole-4-boronic acid pinacol ester, which comprises the following steps: by taking 2, 4-dibromothiazole as an initial raw material, carrying out certain modification on the site 2, 4-dibromothiazole, then converting hydrogen at the site 5 of thiazole into trimethyl silicon by using isopropyl magnesium chloride and trimethylchlorosilane, and finally converting bromine at the site 4 into boronic acid pinacol ester by using a metal organic reagent. The method avoids the use of an expensive palladium catalyst, is simple and convenient in post-treatment, and is suitable for industrial large-scale production.

Description

technical field [0001] The invention belongs to the field of organic chemistry, in particular to a method for preparing 2-substituted thiazole-4-boronic acid pinacol esters. Background technique [0002] The thiazole ring is an important aromatic five-membered heterocyclic ring. The thiazole ring can be obtained by replacing the 3-position carbon atom of the thiophene ring with a nitrogen atom. This type of heterocycle contains nitrogen and sulfur heteroatoms at the same time, which determines that it has abundant electrons, is easy to form hydrogen bonds, can coordinate with non-metal ions, and can stack π-π stacks, generate electrostatic and hydrophobic interactions, etc. Physical and chemical properties such as valence bond interactions [1]. The diverse physical and chemical properties determine that thiazole rings have broad application prospects in many fields such as chemistry, pharmacy, biology, and materials science, so they have also attracted widespread attention....

Claims

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Application Information

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IPC IPC(8): C07F5/02
CPCC07F5/025
Inventor 吕宝瑞郑鹏
Owner DALIAN NETCHEM CHIRAL TECH