Chinese Journal of Organic Chemistry >
Process Development and Scale-Up of (S)-tert-Butyl(6-oxopiperdin-3-yl)carbamate
Received date: 2024-06-06
Revised date: 2024-08-16
Online published: 2024-09-27
Supported by
National Natural Science Foundation of China(22101268); Henan Provincial Natural Science Foundation General Project(242300420180); Henan Provincial Natural Science Foundation General Project(242300420193); Henan Provincial Key R&D and Promotion Special (Science and Technology Tackling) Project(242102230180); Basic Research Fund of Henan Academy of Sciences China(230603001)
An efficient four-step synthesis methodology has been devised for the synthesis of the high-value chiral pharmaceutical building block (S)-tert-butyl(6-oxopiperdin-3-yl)carbamate (1). Commencing with L-pyroglutaminol, p-tosyl (p-Ts) was innovatively employed as the activating and leaving group for the hydroxyl moiety, thereby replacing the methylsulfonyl (Ms) group. Meanwhile, dibenzylamine was successfully substituted for sodium azide as the amine source. This effectively circumventing the utilization of difficult-to-obtain controlled reagents like MsCl and the highly toxic and explosive NaN3. The synthesis process of 1 has been comprehensively optimized, resulting in an impressive total yield of 67% at the hundred-gram scale, while maintaining a purity of 99.4% for the target product. The reagents employed throughout the synthesis route are readily available and cost-effective. The synthesis route is concise and efficient, and the purification method is simple and user-friendly, laying a robust foundation for potential industrial-scale production.
Yongsheng Li , Xiaowen Tang , Xu Li , Peng Yang . Process Development and Scale-Up of (S)-tert-Butyl(6-oxopiperdin-3-yl)carbamate[J]. Chinese Journal of Organic Chemistry, 2025 , 45(1) : 220 -226 . DOI: 10.6023/cjoc202406006
| [1] | Vitaku, E. V.; Smith, D. T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257. |
| [2] | Abdelshaheed, M. M.; Fawzy, I. M.; El-Subbagh, H. I.; Youssef, K. M. Future J. Pharm. Sci. 2021, 7, 188. |
| [3] | Chen, Q.-S.; Li, J.-Q.; Zhang, Q.-W. Pharm. Fronts 2023, 5, e1. |
| [4] | Frolov, N.; Vereshchagin, A. N. Int. J. Mol. Sci. 2023, 24, 2937. |
| [5] | Dowarah, J.; Singh, V. P. Bioorg. Med. Chem. 2020, 28, 115263. |
| [6] | Goel, P.; Alam, O.; Naim, M. J.; Nawaz, F.; Iqbal, M.; Alam, M. I. Eur. J. Med. Chem. 2018, 157, 480. |
| [7] | Rkash, R.; Asati, V.; Kashaw, S. K.; Agarwal, S.; Parwani, D.; Bhattacharya, S.; Mallick, C. Mini-Rev. Med. Chem. 2021, 21, 362. |
| [8] | Sun, W.; Liao, A.; Lei, L.; Tang, X.; Wang, Y.; Wu, J. Chin. Chem. Lett. 2025, 36, 109855. |
| [9] | Marineau, J. J.; Hamman, K. B.; Hu, S.; Alnemy, S.; Mihalich, J.; Kabro, A.; Whitmore, K. M.; Winter, D. K.; Roy, S.; Ciblat, S.; Ke, N.; Savinainen, A.; Wilsily, A.; Malojcic, G.; Zahler, R.; Schmidt, D.; Bradley, M. J.; Waters, N. J.; Chuaqui, C. J. Med. Chem. 2022, 65, 1458. |
| [10] | Johannessen, L.; Henry, S.; Sawant, P.; D’lppolito, A.; Ke, N.; Lefkowitz, A.; Eaton, M.; Dworakowski, W.; Rosario, M.; Hodgson, G. Blood 2021, 138, 1205. |
| [11] | Blair, H. A. Drugs 2023, 83, 1315. |
| [12] | Liu, J.; Solan, R.; Wolk, R.; Plotka, A.; O'Gorman, M. T.; Winton, J. A.; Kaplan, J.; Purohit, V. S. Br. J. Clin. Pharmacol. 2023, 89, 2208. |
| [13] | Zhang, Z.; Wallace, M. B.; Feng, J.; Stafford, J. A.; Skene, R. J.; Shi, L.; Lee, B.; Aertgeerts, K.; Jennings, A.; Rongda, A.; Xu, R.; Kassel, D. B.; Kaldor, S. W.; Navre, M.; Webb, D. R.; Gwaltney II, S. L. J. Med. Chem. 2011, 54, 510. |
| [14] | Grimshaw, C. E.; Jennings, A.; Kamran, R.; Ueno, H.; Nishigaki, N.; Kossaka, T.; Tani, A.; Sano, H.; Kinugawa, Y.; Koumura, E.; Shi, L.; Takeuchi, K. PloS One 2016, 11, e0157509. |
| [15] | Feng, J.; Zhang, Z.; Wallace, M. B.; Stafford, J. A.; Kaldor, S. W.; Kassel, D. B.; Navre, M.; Shi, L.; Skene, R. J.; Asakawa, T.; Takeuchi, K.; Xu, R.; Webb, D. R.; Gwaltney, S. L. J. Med. Chem. 2007, 50, 2297. |
| [16] | Fujita, H.; Taniai, H.; Murayama, H.; Ohshiro, H.; Hayashi, H.; Sato, S.; Kikuchi, N.; Komatsu, T.; Komatsu, K.; Komatsu, K.; Narita, T.; Yamada, Y. Endocr. J. 2014, 61, 159. |
| [17] | Panday, S. K.; Langlois, N. Tetrahedron Lett. 1995, 36, 8205. |
| [18] | Langlois, N.; Van Bac, N.; Dahuron, N.; Delcroix, J.-M.; Deyine, A.; Griffart-Bruned, D.; Chiaroni, A.; Riche, C. Tetrahedron 1995, 51, 3571. |
| [19] | Langlois, N. Tetrahedron Lett. 2002, 43, 9531. |
| [20] | Masse, J.; Langlois, N. Heterocycles 2009, 77, 417. |
| [21] | Thomas, A.; Bhavar, P. K.; Lingam, V. S. P. R.; Joshi, N. K. WO 2004/022536, 2004. |
| [22] | Albers, R.; Ayala, L.; Clareen, S. S.; Delgado Mederos, M. M.; Hilgraf, R.; Hedge, S.; Hughes, K.; Kois, A.; Plantevin-Krenitsky, V.; Mccarrick, M.; Nadolny, L.; Palanki, M.; Sahasrabudhe, K.; Sapienza, J.; Satoh, Y.; Sloss, M.; Sudbeck, E.; Wright, J. WO 2006/076595, 2006. |
| [23] | Do, S.; Hu, H.; Kolesnikov, A.; Tsui, V. H.; Wang, X. WO 2014/001377, 2014. |
| [24] | Marineau, J. J.; Chuaqui, C.; Ciblat, S.; Kabro, A.; Piras, H.; Whitmore, K. M.; Lund, K.-L. WO 2019/143719, 2019. |
| [25] | Marineau, J. J.; Chuaqui, C. WO 2020/093011, 2020. |
| [26] | Li, L.; Zhang, Y. CN 104098563, 2014. |
| [27] | Huang, S.-B.; Nelson, J. S.; Weller, D. D. J. Org. Chem. 1991, 56, 6007. |
| [28] | Ghosh, A. K.; Leshchenko-Yashchuk, S.; Anderson, D. D.; Bal- dridge, A.; Noetzel, M.; Miller, H. B.; Tie, Y.; Wang, Y.-F.; Koh, Y.; Weber, I. T.; Mitsuya, H. J. Med. Chem. 2009, 52, 3902. |
| [29] | Langlois, N. Org. Lett. 2002, 4, 185. |
| [30] | Tan, H.; Reed, M.; Gahm, K. H.; King, T.; Seran, M. D.; Bostick, T.; Luu, V.; Semin, D.; Cheetham, J.; Larsen, R.; Martinelli, M.; Reider, P. Org. Process Res. Dev. 2008, 12, 58. |
/
| 〈 |
|
〉 |
