1-Boc-4-甲基哌啶a位的酰化反应研究任务书
2020-05-21 10:05
1. 毕业设计（论文）的内容和要求
查阅相关文献资料，能够读懂英文文献；
综合文献中的实验方法，设计与课题相关的条件实验；
开展各个不同的条件实验，在实际操作过程中要能够分析并解决突发问题，能够对不同的实验结果进行分析对比；
2. 参考文献
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[1] 王刚 《阿加曲班原料药中的杂质控制》 浙江大学 2013年 [2] Asymmetric Substitutions of 2-Lithiated N-Boc-piperidine and N-Boc-azepine by Dynamic Resolution[J], Chem. Eur. J. 2010, 16: 4082~4090; [3] 袁丽娟, 刘爱民, 刘蕾. 新型凝血酶抑制剂阿加曲班[J]. 中国新药杂志, 2005, 14(2): 230~234. [4] 许俊堂. 阿加曲班临床应用的进展[J]. Chinese Journal of Thrombosis and Hemostasis. 2007, 12(4): 180~182. [5] Kadouri P C, Comesse S. Recent Advances in Asymmetric Synthesis of Pipecolic Acid and Derivatives[J]. Amino Acids. 2005, 29(2): 101~130. [6] 李振东, 樊军, 张宗伟. 哌啶酸及其衍生物合成的研究进展[J]. 化学通报, 2006, 69: 1~7. [7] Alegret C, Santacana F, Riera A. Enantioselective Synthesis of Trans-4-methylpipecolic acid[J]. J Org Chem. 2007, 72(20): 7688~7692. [8] Beak, P. amp; Lee, W. K. α-Lithioamine synthetic equivalents from dipole-stabilized carbanions. The tert-BOC group as an activator for α'-lithiation of carbamates[J]. Tetrahedron Lett. 1989, 30: 1197~1200. [9] Shuman R T, Ornstein P L, Paschal J W, et al. An Improved Synthesis of Homoproline and Derivatives[J]. J Org Chem. 1990, 55: 738~741. [10] Cossy J, Belotti D. Direct Diastereoselective Synthesis of (#177;)-cis- and (#177;)-trans-4- methylpipecolic Acid and Derivatives[J]. Tetrahedron Letters. 2001, 42: 2119~2120. [11] Fareed, J. amp; Jeske, W. P. Small-molecule direct antithrombins: argatroban[J]. Best Pract. Res., Clin. Haematol. 2004, 17: 127~138. [12] Kathleen M. Bertini Gross, Young M. Jun, and Peter Beak, Asymmetric Deprotonations: Lithiation of N-(tert-Butoxycarbonyl)indoline with sec-Butyllithium/(-)-Sparteine[J], J. Org. Chem. 1997, 62: 7679~7689. [13] Darren Stead, Giorgio Carbone, Peter O#8217;Brien, Asymmetric Deprotonation of N-Boc Piperidine: React IR Monitoring and Mechanistic Aspects[J], J. Am. Chem. Soc. 2010, 132, 7260~7261. [14] Nadeem S. Sheikh, Daniele Leonori, Graeme Barker, An Experimental and in Situ IR Spectroscopic Study of the Lithiation#8722;Substitution of N-Boc-2-phenylpyrrolidine and -piperidine: Controlling the Formation of Quaternary Stereocenters, J. Am. Chem. Soc. 2012, 134: 5300~5308. [15] Xiabing Li, Daniele Leonori, Nadeem S. Sheikh, Synthesis of 1-Substituted Tetrahydroisoquinolines by Lithiation and Electrophilic Quenching Guided by In Situ IR and NMR Spectroscopy and Application to the Synthesis of Salsolidine, Carnegine and Laudanosine[J], Chem. Eur. J. 2013, 19: 7724~7730.
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3. 毕业设计（论文）进程安排
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2016.02.22-2016.03.10 |
查阅国内外有关文献，做文献综述；完成外文翻译；拟定实验方案。 |
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2016.03.10-2016.05.20 |
按照实验要求进行各种实验工作。 |
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2016.05.20-2016.06.01 |
进行实验数据的处理，补充有关实验，开始撰写论文。 |
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2016.06.01-2016.06.10 |
完成论文，准备答辩。 |
