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A kind of preparation method of n-tert-butoxycarbonyl-4-nitropiperidine

A technology of hydroxy-tert-butoxycarbonylpiperidine and tert-butoxycarbonyl, which is applied in the field of synthesis of N-tert-butoxycarbonyl-4-nitropiperidine, which can solve the disadvantages of large-scale synthesis, long reaction steps and low synthesis yield problems such as shortening the reaction time, increasing the yield, and simple operation

Active Publication Date: 2016-08-10
上海药明康德新药开发有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It mainly solves the current technical problems such as low synthesis yield, long reaction steps, overly complicated operation, and unfavorable large-scale synthesis.

Method used

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  • A kind of preparation method of n-tert-butoxycarbonyl-4-nitropiperidine
  • A kind of preparation method of n-tert-butoxycarbonyl-4-nitropiperidine

Examples

Experimental program
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Effect test

Embodiment 1

[0016] Example 1: Add raw material 1 (100 g, 0.496 mol) to the reaction flask, dissolve triphenylphosphine (156 g, 0.596 mol) and imidazole (405 g, 0.596 mol) in anhydrous tetrahydrofuran (400 ml), keep The temperature is 2-3°C, and then iodine (151g, 0.596mol) is dissolved in anhydrous tetrahydrofuran and dropped into the reaction solution, and the temperature during the dropwise addition should not exceed 12°C. After addition, return to room temperature and stir overnight. Using petroleum ether: ethyl acetate (volume ratio) = 5:1 as the developer, the Rf value of the product is around 0.5. After the detection reaction is completed, add 10% NaHSO by mass fraction when cooling to 8°C 3 (80mL). Spin the solution to dryness, then add n-hexane (350mL), filter with suction, pour off the upper clear layer first, then filter off the solid at the bottom, and wash the filter residue with a large amount of n-hexane. The supernatant was washed with 1mol / L hydrochloric acid to neutra...

Embodiment 2

[0017] Example 2: Add raw material 1 (1000 g, 4.96 mol) to the reaction flask, dissolve triphenylphosphine (1560 g, 5.96 mol) and imidazole (4050 g, 5.96 mol) in anhydrous tetrahydrofuran (4000 ml), keep The temperature is 2-3°C, and then iodine (1510g, 5.96mol) is dissolved in anhydrous tetrahydrofuran and added dropwise to the reaction solution, and the dropwise addition process controls the temperature not to exceed 12°C. After addition, return to room temperature and stir overnight. Using petroleum ether: ethyl acetate (volume ratio) = 5:1 as the developer, the Rf value of the product is around 0.5. After the detection reaction is completed, add 10% NaHSO by mass fraction when cooling to 8°C 3 (800mL). Spin the solution to dryness, then add n-hexane (4000mL), filter with suction, first pour off the upper clear layer, then filter off the solid at the bottom, and wash the filter residue with a large amount of n-hexane. The supernatant was washed with 1mol / L hydrochloric ...

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Abstract

The invention relates to a preparing method of N-t-butyloxycarboryl-4-nitro piperidine. The method mainly solves the technical problems that in an existing synthetic process, the route is long, yield is low, reaction is not easy to control, experimental operation is inconvenient, and the like. According to the method, N-t-butyloxycarboryl-4-hydroxy piperidine is used as raw material to prepare N-t-butyloxycarboryl-4-iodine piperidine, and further the target product is obtained through the substitution reaction. The N-t-butyloxycarboryl-4-nitro piperidine obtained with the method is a useful intermediate or product used for synthesis of various kinds of drugs.

Description

technical field [0001] The present invention relates to the synthesis method of N-tert-butoxycarbonyl-4-nitropiperidine. Background technique [0002] N-tert-butoxycarbonyl-4-nitropiperidine is a useful intermediate in organic synthesis. It has been described in patents WO2009126515, JP2008273847 and WO2007055514, and is widely used in Michael addition, such as WO2007052843, US20060217417 and WO2003048124. It has also been used to synthesize anti-HIV drugs recently, such as WO9744037. At present, there are mainly two methods for the synthesis of such compounds: the first one uses N-tert-butoxycarbonyl-piperidone as a raw material to synthesize oxime, and then oxidizes to obtain N-tert-butoxycarbonyl-4-nitropiperidine ketone. The method is relatively complicated to operate and the yield is not high. The second leads directly to the product by oxidation of N-tert-butoxycarbonyl-4-aminopiperidone. Although there are few steps and simple operation, the yield is only 22%. In...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D211/38
Inventor 张旭华郭爱新马建义姜鲁勇马汝建
Owner 上海药明康德新药开发有限公司