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Synthesis method of 3-amino-4-phenylboronic acid pinacol ester

A technology for chlorophenylboronic acid and pinacol ester, which is applied in the field of synthesis of 3-amino-4-chlorophenylboronic acid pinacol ester, can solve the problems of low yield and many steps, and achieves cheap raw materials and purification. Simple, productivity-enhancing effects

Inactive Publication Date: 2017-11-24
GL BIOCHEM SHANGHAI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The purpose of this invention is to provide a kind of synthetic method of 3-amino-4-chlorophenylboronic acid pinacol ester, mainly solve the present synthetic method step more, the technical problem that productive rate is lower

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0010] step 1:

[0011] Add 5-bromo-2-chloronitrobenzene (11.8 g, 50.0 mmol), double pinacol borate (12.7 g, 50.0 mmol), potassium acetate (9.8 g, 100.0 mmol) and 1 , 4-dioxane (, 120 mL) and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (1.8 g, 2.5 mmol). The reaction liquid was heated to reflux at 110° C. for 3 hours under the protection of nitrogen gas. Cool to room temperature, distill off the solvent under reduced pressure, dissolve the residue with ethyl acetate (200 mL), filter to remove solid impurities, wash the filtrate with water (60 mL) and saturated brine (60 mL), dry over sodium sulfate, and filter. The filtrate was spin-dried, and the crude product was separated by silica gel column chromatography (petroleum ether: ethyl acetate volume ratio = 10:1) to obtain a yellow solid, Compound 1 (13.0 g, 45.9 mmol, 92%). 1 H NMR (300 MHz, CDCl 3 ): 1.35 (s, 12 H), 7.54 (d, J = 6.0 Hz, 1 H),7.89 (d, J = 6.0 Hz, 1 H), 8.10 (s, 1 H);

[0012] Step 2:

...

Embodiment 2

[0014] Embodiment 2: the first step reaction temperature is 90°C, the reaction time is 4 hours, the second step reaction temperature is 80°C, and the reaction time is 3 hours; the rest are the same as in Example 1.

Embodiment 3

[0015] Embodiment 3: the first step reaction temperature is 130°C, the reaction time is 2 hours, the second step reaction temperature is 130°C, and the reaction time is 1 hour; the rest are the same as in Example 1.

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PUM

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Abstract

The invention relates to a synthesis method of 3-amino-4-phenylboronic acid pinacol ester. The method mainly solves the technical problem to improve the yield. The synthesis method provided by the invention comprises the following steps of under the catalysis effect of [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium, 5-bromine-2-chloronitrobenzene reacts with bis(pinacolato)diboron in 1,4-dioxane to obtain a compound ; the compound 1 reacts with ammonium chloride and ion powder in mixed solution of ethyl alcohol and water; nitro is reduced into amino; a target compound 2 is generated. As a high-price medicine intermediate, the 3-amino-4- phenylboronic acid pinacol ester is widely applied to the pharmacy industry.

Description

technical field [0001] The present invention relates to the synthesis of 3-amino-4-chlorophenylboronic acid pinacol ester. Background technique [0002] 3-Amino-4-chlorophenylboronic acid pinacol ester (CAS: 850567-56-5), as a very important pharmaceutical intermediate, is widely used in the pharmaceutical industry. In 2014, Di Qiu et al. reported the synthesis methods of compound 1 and target compound 2 on J. Org. Chem. The yields were 52% and 74%, respectively. Contents of the invention [0003] The purpose of the present invention is to provide a kind of synthetic method of 3-amino-4-chlorophenylboronic acid pinacol ester, mainly solves the technical problem that present synthetic method step is more, and productive rate is lower. [0004] The technical scheme of the present invention is: a synthetic method of 3-amino-4-chlorophenylboronic acid pinacol ester, which is characterized in that it comprises the following steps: the first step, in [1,1'-bis(diphenylphosphine...

Claims

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Application Information

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IPC IPC(8): C07F5/02
CPCC07F5/025
Inventor 徐红岩马敬祥
Owner GL BIOCHEM SHANGHAI