<sup id="6igwk"><center id="6igwk"></center></sup>
<acronym id="6igwk"><small id="6igwk"></small></acronym>
<acronym id="6igwk"></acronym>
<acronym id="6igwk"><div id="6igwk"></div></acronym>
<rt id="6igwk"><small id="6igwk"></small></rt>
<rt id="6igwk"><optgroup id="6igwk"></optgroup></rt>
<acronym id="6igwk"><center id="6igwk"></center></acronym>
<rt id="6igwk"><small id="6igwk"></small></rt>

Synthesis of N-Boc 4-piperidone

May 17,2022

Reactions of N-Boc-piperidin-4-one with aromatic aldehydes afforded nitrogen-containing 1,5-diketones in the form of products of intramolecular aldol cyclization, like aza derivatives of tricyclo [7.3.1.02,7]-tridecanone system underlying naturally occurring limonoids. With o-phenylenediamine they enter into a domino-reaction leading to the formation of hydrobenzimidazo[2,1-e] acridine structure. N-Boc-piperidin-4-one in Michael reaction with diarylidenecyclohexanones forms 1,5-diketones undergoing cyclization into hydroxypyran structure.

79099-07-3.gif

Synthesis

We have optimized a Pd-catalyzed enantioselective borylative migration of an alkenyl nonaflate derivative of the simple precursor, N-Boc 4-piperidone. This anomalous borylation reaction lends access to a chiral optically enriched piperidinyl allylic boronate that can beemployed in carbonyl allylboration and stereoselective cross-coupling to produce substituted dehydro-piperidines related to numerous pharmaceutical agents.

A systematic fine-tuning of reaction conditions revealed that diethyl ether and the green solvent cyclopentyl methyl ether are suitable reaction solvents providing the highest enantioselectivity (up to 92% ee) under a low catalyst loading of 3 mol%. Optimization of the aldehyde allylboration step led to higher yields with further solvent economy. The multigram-scalability of the entire process was demonstrated under the reaction conditions that provide optimal atom-economy and efficiency

Current methods for the stereoselective preparation of polysubstituted piperidines can be classified into three general synthetic approaches about common synthetic strategies for the preparation of chiral piperidines:

 

Scheme1:Synthetic applications of heterocyclic allylic boronates, prepared by a catalytic enantioselective borylative migration.


Scheme2:Optimal conditions for the racemic catalytic borylative migration of 8

The use of alternate substrates embedding an alkenyl nonaflate or a carboxybenzyl carbamate did not lead to a significant increase of enantioselectivity; however, substrate 8 combining an alkenyl nonaflate with N-Boc protection led to a higher yield. Moreover, it is noteworthy that compared to that of substrate 2, the preparation of substrate 8 is higher-yielding and more cost-effective because perfluorobutanesulfonyl fluoride is a less expensive reagent than phenyl triflimide, and the chromatographic purification is easier. Furthermore, compared to a N-Cbz group, which is cleaved by catalytic hydrogenation, removal of a N-Boc[1] protecting group is orthogonal to the alkene in the allylboration products. Therefore, although

N-Cbz substrate 9 provided a lower proportion of undesired alkenyl boronate 11, it was decided to employ substrate 8 for subsequent optimization. The undesired alkenyl boronate side-product can be removed with ease, unreacted, after the subsequent aldehyde allylboration step.[2]

Application

The development of new, efficient and economical methods for the preparation of functionalized, optically enriched piperidines is important in the field of drug discovery where this class of heterocycles is often deemed a privileged structure.

Handling and storage

Clarify that the liquid is dark yellow. If inhaled, move the patient to fresh air., If breathing stops, perform artificial respiration. Rinse with soap and plenty of water. Wash eyes with water carefully. Never feed anything to an unconscious person., Rinse your mouth with water.

1.Inhalation if inhaled, move the patient to fresh air. If breathing stops, perform artificial respiration.

2.Skin contact wash with soap and plenty of water.

3.Eye contact wash eyes with water carefully.

4.Do not feed anything to an unconscious person. Rinse your mouth with water.

Store in a cool place. Keep the container closed and store in a dry and ventilated place. Open containers must be carefully resealed and kept upright to prevent leakage.

1. Do not allow the product to enter the sewer.

2. Place in a suitable closed container for disposal.

References

[1], "Nitrogen-Containing 1,5-Diketones Based on N-Boc-Piperidin-4-one, Synthesis, Intramolecular Cyclization, and Reaction with o-Phenylenediamine,".

[2]Kim Y. & Hall D. G., "Optimization and multigram scalability of a catalytic enantioselective borylative migration for the synthesis of functionalized chiral piperidines," Organic & Biomolecular Chemistry, Vol.14, No.20(2016), pp.4739-4748.

  • Related articles
  • Related Qustion
  • What is N-(tert-Butoxycarbonyl)-4-piperidone? Jan 13, 2020

    N-boc-4-piperidone is the derivative of 4-piperidone and is an important pharmaceutical intermediate. N-boc-4-piperidone can be used to synthesize angiotensin-converting enzyme inhibitor (ACEI) (Trandolapril), anti-AIDS protease inhibitor.

See also

With the rapid development of domestic silicone industry, the consumption of silicone rubber and silicone resin is also increasing. As an important component of silicone rubber and silicone resin, the....

May 13,2022Organic Synthesis Intermediate

Acetone (ACE one) is an important organic raw material, which is mainly used to produce cellulose acetate film, plastic and coating solvent.....

May 17,2022Organic reagents

<sup id="6igwk"><center id="6igwk"></center></sup>
<acronym id="6igwk"><small id="6igwk"></small></acronym>
<acronym id="6igwk"></acronym>
<acronym id="6igwk"><div id="6igwk"></div></acronym>
<rt id="6igwk"><small id="6igwk"></small></rt>
<rt id="6igwk"><optgroup id="6igwk"></optgroup></rt>
<acronym id="6igwk"><center id="6igwk"></center></acronym>
<rt id="6igwk"><small id="6igwk"></small></rt>
国产青青操,国产特黄A片免费播放,蜜芽MIYA737.MON牢记跳转接口免费,国产精品久久久久妇女网站
国产一区二区电影| 无码粉嫩小泬无套在线观看动态图| 国产亚洲人成网站在线观看播放| 蜜桃成熟1997全集| 国产黄在线播放免费观看| 97在线观看| 中年人妻丰满av无码久久不卡| 乱人伦XXXX中国| 最近中文字幕完整视频高清1| 亚洲Av无码Av另类专区| 人妻2乱3伦| 粉红色火烈鸟| 日本三级在线播放线观看网站| 欧美午夜电影| 秋葵app免费下载软件大全| 日日夜夜狠狠操| 18禁纯肉高黄无码动漫在线| 少妇被粗大后进猛XX动态图| av无码中文字幕| 色欲av麻豆精品一区二区三区| 色偷偷人人澡人人添老妇人| 亚洲精品国内少妇30P| 亚洲色婷婷久久综合一区| 亚洲黄久久| 少妇无码第一区二区三区色戒| 亚洲欧美日韩综合| 日韩三级在线| 亚洲伊人色宗网一区二区| 日本在线视频| 青海花儿歌曲1000首| 午夜大胆裸A级人体片| 成人久久久久人妻一区| 国产一二三2021精字窝| 免费视频完整版软件下载| 中文无码一区二区不卡ΑV| 中日韩美一级毛片天天摸| 蜜臀AV无码乱码国产精品| 日本十八禁一区二区三区| 久久www免费人成一看片| 久久免费高潮毛片A片| AV无码亚洲不卡播放网站| http://www.tiffanysale.net.cn http://www.wingwin.com.cn http://www.tsjhd.com.cn