Citation: Zhu Lanping, Zhao Shuai, Cang Zhipeng, Zhou Andi, Chen Xin. An Efficient Method for the Synthesis of 2-Methyl-1-substituted-phenyl-2-propylamines[J]. Chinese Journal of Organic Chemistry, ;2018, 38(7): 1695-1702. doi: 10.6023/cjoc201801029 shu

An Efficient Method for the Synthesis of 2-Methyl-1-substituted-phenyl-2-propylamines

School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164

Corresponding author: Chen Xin, xinchen@cczu.edu.cn
Received Date: 21 January 2018
Revised Date: 7 March 2018
Available Online: 4 July 2018
Fund Project: the National Natural Science Foundation of China 21272029Project supported by the National Natural Science Foundation of China (No. 21272029)

Figures(3)

2-Methyl-1-substituted-phenyl-2-propylamines are key intermediates for synthesizing the β₂ adrenoceptor agonists. A series of 2-methyl-1-substituted-phenyl-2-propylamines have been synthesized starting from substituted benzyl chlorides. Isobutyronitrile was alkylated with benzyl chloride, and the resulting 2-methyl-1-aryl-2-butylcynide was hydrolyzed to give the corresponding acid. Curtius rearrangement of the acid and catalytic hydrolgenation of the resulting Cbz-protected amine afforded the title compound. The method is simple and safe to operate, the raw materials are readily available and the overall yields are satisfactory. This method is suitable for the synthesis of 2-methyl-2-(2-methylphenyl)-phenyl-2-propylamine and various kinds of derivatives.
- 2-methyl-1-substituted-phenyl-2-propylamine,
- β₂ adrenoceptor agonist,
- Curtius rearrangement,
- synthesis
1. [1]
  Pasternak, A; Goble, S. D.; Reynalda, K. Bioorg. Med. Chem. Lett. 2009, 19, 6237. doi: 10.1016/j.bmcl.2009.08.076
2. [2]
  Southers, J. A.; Bauman, J. N.; Kalgutkar, A. S. Med. Chem. Lett. 2010, 1, 219. doi: 10.1021/ml100058w
3. [3]
  Jesudason, C. D.; Trankle, W. G.; Shuker, A. J. Med. Chem. Lett. 2011, 2, 583. doi: 10.1021/ml200071k
4. [4]
  Czeskis, B. A.; Wheeler, W. J.; Clodfelter, D. K. J. Labelled Compd. Radiopharm. 2006, 49, 663. doi: 10.1002/(ISSN)1099-1344
5. [5]
  Tautermann, C. S.; Pautsch, A. Med. Chem. Lett. 2011, 2, 414. doi: 10.1021/ml100247s
6. [6]
  Hoenke, C.; Bouyssou, T.; Konetzki, I. Bioorg. Med. Chem. Lett. 2009, 19, 6640. doi: 10.1016/j.bmcl.2009.10.013
7. [7]
  Hoenke, C.; Bouyssou, T.; Konetzki, I. Bioorg. Med. Chem. Lett. 2010, 20, 1410. doi: 10.1016/j.bmcl.2009.12.087
8. [8]
  Goldfuss, B.; Denisenko, D.; Kulhanek, J. Chem.-Eur. J. 2004, 10, 4252. doi: 10.1002/(ISSN)1521-3765
9. [9]
  Ritter, J. J.; Minieri, P. P. J. Am. Chem. Soc. 1948, 70, 4045. doi: 10.1021/ja01192a022
10. [10]
  Florvall, L.; Fagervall, I.; Ask, A.-L.; Ross, S. B. J. Med. Chem. 1986, 29, 2250. doi: 10.1021/jm00161a020
11. [11]
  Wang, J. B.; Sun, X. Q.; Chen, X. Chin. J. Org. Chem. 2013, 33, 634 (in Chinese).
12. [12]
  Ling. P. X.; Fang, S. L.; Yin, X. S.; Chen, K.; Sun, B. Z.; Shi, B. F. Chem.-Eur. J. 2015, 21, 17503. doi: 10.1002/chem.201502621
13. [13]
  Espino, C. G.; Fiori, K. W.; Bois, J. D. J. Am. Chem. Soc. 2004, 126, 15378. doi: 10.1021/ja0446294
14. [14]
  Ninomiya, K.; Shioiri, T.; Yamada, S. Tetrahedron 1974, 30, 2151. doi: 10.1016/S0040-4020(01)97352-1
15. [15]
  Jasys, V. J.; Lombardo, F.; Volkmann, R. A. J. Am. Chem. Soc. 2000, 122, 466. doi: 10.1021/ja992652x
16. [16]
  Fleming, F. F.; Ghosh, S.; Steward, O. W. J. Org. Chem. 2008, 73, 2803. doi: 10.1021/jo702681e
17. [17]
  Jiang, X.; Hartwig, J. F. Angew. Chem., Int. Ed. 2017, 56, 8887. doi: 10.1002/anie.v56.30
18. [18]
  Spectral data for the Curtius rearrangement intermediate 2-methyl-1-(2-methylphenyl)-2-propyl isocyanate: ¹H NMR (300 MHz, CDCl₃) δ: 7. 18~7. 17 (m, 4H), 2. 84 (s, 2H), 2. 36 (s, 3H), 1. 38 (s, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 137. 34, 135. 23, 131. 59, 130. 73, 127. 11, 125. 68, 122. 84, 59. 32, 45. 31, 30. 65, 20. 38; HRMS (ESI, positive) calcd for C₁₂H₁₅NO[M+H]⁺ 190. 1226, found 190. 1306.
19. [19]
  Jung, M. E.; Amico, D. C. J. Am. Chem. Soc. 1995, 117, 7379. doi: 10.1021/ja00133a011
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