Method for synthesizing N-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester

A technology of tert-butoxycarbonyl and tetrahydropyridine, which is applied in the field of chemical synthesis, can solve the problems of low yield, long cycle and high cost, and achieve the effects of short process route, high yield and high product purity

Inactive Publication Date: 2011-08-17
LANZHOU MINUO BIOLOGICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But the phenylbis(trifluoromethanesulfonyl)imide that adopts in this document is that raw material cost is higher, and nitrogen-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol Synthesis of esters adds cost and yields are lower
At the same time, the post-treatment process of this method adopts the method of column chromatography, which has high cost and long period.

Method used

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  • Method for synthesizing N-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester
  • Method for synthesizing N-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] (1) Synthesis of nitrogen-4-pyridine bis(trifluoromethanesulfonyl)imide

[0039] Dissolve 4-aminopyridine and triethylamine in a molar ratio of 1:3 in dried methylene chloride (the amount used is 10 times the mass of 4-aminopyridine), and slowly add the molar amount of 4-aminopyridine dropwise at 0°C 2.2 times of trifluoromethanesulfonic anhydride, dropwise for 1 hour, stir at room temperature for 1 hour after dropping, cool to 0°C, wash the solution with water and saturated brine, dry the dichloromethane layer with anhydrous sodium sulfate, and evaporate to dryness , in crude nitrogen-4-pyridine bis(trifluoromethanesulfonyl)imide. The crude product was recrystallized from n-hexane to obtain the pure product with a yield of 80%.

[0040] (2) Synthesis of tert-butyl 3,6-dihydro-4-[[(trifluoromethyl)sulfonyl]oxy]-1(2H)-pyridinecarboxylate

[0041] Dissolve diisopropylamine in dry tetrahydrofuran (the amount of tetrahydrofuran is 10 times the mass of diisopropylamine), a...

Embodiment 2

[0048] (1) Synthesis of nitrogen-4-pyridine bis(trifluoromethanesulfonyl)imide

[0049] Dissolve 4-aminopyridine and triethylamine in a molar ratio of 1:3.5 in dried methylene chloride (the amount used is 10 times the mass of 4-aminopyridine), and slowly add the molar amount of 4-aminopyridine dropwise at 0°C 2.5 times the amount of trifluoromethanesulfonic anhydride, the dropwise addition time is 2 hours, after the dropping is completed, stir at room temperature for 1 hour; cool to about 0°C, wash the solution with water and saturated saline, dry the dichloromethane layer with anhydrous sodium sulfate, evaporate Dry to get the crude product nitrogen-4-pyridine bis(trifluoromethanesulfonyl)imide, the crude product nitrogen-4-pyridine bis(trifluoromethanesulfonyl)imide was recrystallized with n-hexane to obtain pure product, yield 85% .

[0050] (2) Synthesis of tert-butyl 3,6-dihydro-4-[[(trifluoromethyl)sulfonyl]oxy]-1(2H)-pyridinecarboxylate

[0051] Dissolve diisopropylam...

Embodiment 3

[0058] (1) Synthesis of nitrogen-4-pyridine bis(trifluoromethanesulfonyl)imide

[0059] Dissolve 4-aminopyridine and triethylamine in dry dichloromethane at a molar ratio of 1:4 (the amount of dichloromethane is 13 times the mass of 4-aminopyridine), slowly add 4 -Trifluoromethanesulfonic anhydride with 2.2 times the molar weight of aminopyridine, the dropwise addition time is 1 hour; after the dropping is completed, stir at room temperature for 1 hour, cool to 5°C, wash the solution with water and saturated brine, and wash the dichloromethane layer with anhydrous sulfuric acid Drying over sodium and evaporating to dryness gave the crude product nitrogen-4-pyridine bis(trifluoromethanesulfonyl)imide, and the crude product nitrogen-4-pyridine bis(trifluoromethanesulfonyl)imide was recrystallized with n-hexane to obtain the pure product, The yield is 81%.

[0060] (2) Synthesis of tert-butyl 3,6-dihydro-4-[[(trifluoromethyl)sulfonyl]oxy]-1(2H)-pyridinecarboxylate

[0061] Diss...

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Abstract

The invention provides a novel method for synthesizing N-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester, which belongs to the technical field of chemical synthesis. The method comprises the following steps of: obtaining a target product, namely the N-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester through a three-step reaction by taking N-(tert-butoxycarbonyl)-4-piperidone, 4-aminopyridine, trifluoromethanesulfonic anhydride, n-butyl lithium, bis(pinacolato)diboron, triethylamine, diisopropylamine and potassium acetate as raw materials,dichloromethane, tetrahydrofuran and dioxane as solvents, and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) as a catalyst; and characterizing data through liquid chromatogram, nuclear magnetic spectrum and mass spectrum. By the method, the production period is short, the synthetic cost is low, a synthetic process is safe and reliable, and a post-treatment method is simple, convenient and quick; and the yield of a product is high (51 to 58 percent) and the purity of the product is high (98.2 to 99.6 percent).

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis and relates to a new method for synthesizing nitrogen-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester. Background technique [0002] Nitrogen-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester is an important pharmaceutical intermediate, the mother core intermediate of many drugs, and is widely used in many pharmaceuticals at home and abroad There is a wide range of applications in the synthesis of intermediates and has a large market. [0003] "Bioorganic & Medicinal Chemistry Letters" (Bioorganic & Medicinal Chemistry Letters) 2008 No. 18 disclosed a nitrogen-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester The synthesis method is to use nitrogen-tert-butoxycarbonyl-4-piperidone as the starting material, and phenyl bis(trifluoromethanesulfonyl)imide to obtain 3,6 -Dihydro-4-[[(trifluoromethyl)sulfonyl]ox...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02
Inventor 钟炎军陈林
Owner LANZHOU MINUO BIOLOGICAL TECH
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