91419-52-2 4-氰基哌啶-1-羧酸叔丁酯

• [1] Patent: WO2017/83867, 2017, A1. Location in patent: Paragraph 00352 [2] Patent: WO2015/144290, 2015, A1. Location in patent: Page/Page column 67 [3] Journal of Medicinal Chemistry, 2016, vol. 59, # 3, p. 1078 - 1101 [4] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 19, p. 5910 - 5915 [5] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 1, p. 119 - 124 [6] Patent: WO2008/75110, 2008, A1. Location in patent: Page/Page column 126 [7] Journal of Medicinal Chemistry, 2003, vol. 46, # 25, p. 5512 - 5532 [8] Patent: WO2011/71716, 2011, A1. Location in patent: Page/Page column 85 [9] Patent: US6518284, 2003, B2 [10] Patent: US4760158, 1988, A [11] Patent: US6248755, 2001, B1 [12] Patent: WO2009/10479, 2009, A2. Location in patent: Page/Page column 94 [13] Patent: WO2004/99178, 2004, A1. Location in patent: Page 37 [14] Patent: US2007/238723, 2007, A1. Location in patent: Page/Page column 44-45 [15] Patent: WO2014/150344, 2014, A1. Location in patent: Page/Page column 56 [16] Patent: US2015/31674, 2015, A1. Location in patent: Paragraph 0367; 0581 [17] Patent: EP1714961, 2006, A1. Location in patent: Page/Page column 19

合成路线 3（3. 合成：91419-52-2）

产率：73% 合成条件：With potassium hexafluorophosphate; tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen; 1,1,1,3,3,3-hexamethyl-disilazane In acetonitrile at 30℃; for 8 h; 实验步骤：在100ml烧瓶中加入30mL乙腈，10mmol HMDS，0.4mmol TEMPO，0.4mmol KPF6和0.6mmol TBN。 空气被氧气取代。 将混合物在预热的水浴中加热至30℃，缓慢加入4mmol N-Boc-4-哌啶甲醛（如式（1-8）所示）8小时。 将反应混合物与硫代硫酸钠溶液一起搅拌并用乙醚萃取。 分离有机层，减压蒸馏除去溶剂，并将残余物进行柱色谱。 将混合物以1：100的乙酸乙酯/石油醚的体积比搅拌。收集含有标题化合物的洗脱液，蒸发溶剂，得到N-Boc-4-哌啶甲腈，分离收率为70％。 反应程序与实施例20相同，不同之处在于所用乙腈的量为80mL，并且N-Boc-4-哌啶甲腈的分离产率为73％。 参考文献：

• [1] Synlett, 2009, # 20, p. 3378 - 3382 [2] Journal of Organic Chemistry, 2012, vol. 77, # 20, p. 9334 - 9337,4 [3] Journal of Organic Chemistry, 2012, vol. 77, # 20, p. 9334 - 9337 [4] Patent: CN105481624, 2016, A. Location in patent: Paragraph 0041; 0042 [5] Advanced Synthesis and Catalysis, 2016, vol. 358, # 7, p. 1157 - 1163 [6] RSC Advances, 2017, vol. 7, # 3, p. 1484 - 1489 [7] Synlett, 2011, # 15, p. 2223 - 2227 [8] Synthesis (Germany), 2015, vol. 47, # 23, p. 3758 - 3766