A practical one-pot process for α-amino aryl ketone synthesis

Tetrahedron Letters

Volumn 46, Issue 49, 2005, Pages 8587-8589

  Conrad, Karen ^a   Hsiao, Yi ^a   Miller, Ross ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Amino aryl ketone synthesis; Grignard arylation; Weinreb amide

Indexed keywords

KETONE DERIVATIVE; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE;

ARTICLE; ARYLATION; METALLATION; PROTON TRANSPORT; SYNTHESIS;

EID: 27644566720     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2005.09.183     Document Type: Article

References (26)

1. L.E. Fisher, and J.M. Muchowski Org. Prep. Proc. Int. 22 1990 399
2. B.T. O'Neill B.M. Trost I. Fleming Comprehensive Organic Synthesis Vol. 1 1991 Pergamon Press Oxford 397
3. M.T. Reetz, M.W. Drewes, K. Lenick, A. Schmitz, and X. Holdgrun Tetrahedron: Asymmetry 1 1990 375
4. M.P. Sibi Org. Prep. Proc. Int. 25 1993 15
5. J. Singh, N. Satyamurthi, and I.S. Aidhen J. Prakt. Chem. 342 2000 340
6. P. Knochel, M. Abarbri, and F. Dehmel Tetrahedron Lett. 40 1999 7449
7. J.L. Leazer, R. Cvetovich, F. Tsay, U. Dolling, T. Vickery, and D. Bachert J. Org. Chem. 68 2003 3695
8. D.A. Nugiel, K. Jacobs, T. Worley, M. Patel, R.F. Kaltenbach III, D.T. Meyer, P.K. Jadhav, G.V. De Lucca, T.E. Smyser, R.M. Klabe, L.T. Bacheler, M.M. Rayner, and S.P. Seitz J. Med. Chem. 39 1996 2156
9. A.K. Ghosh, W.M. Liu, Y.B. Xu, and Z.D. Chen Angew. Chem., Int. Ed. 35 1996 74
10. A. Datta, J.S.R. Kumar, and S. Roy Tetrahedron 57 2001 1169
11. J.G. Knight, S.W. Ainge, A.M. Harm, S.J. Harwood, H.I. Maughan, D.R. Armour, D.M. Hollinshead, and A.A. Jaxa-Chamiec J. Am. Chem. Soc. 122 2000 2944
12. A.C. Bohnstedt, J.V.N.V. Prasad, and D.H. Rich Tetrahedron Lett. 34 1993 5217
13. M. Seki, and K. Matsumoto Tetrahedron Lett. 37 1996 3165
14. Y. Satoh, and J. Moliterni Synlett 1998 528
15. M.R. Angelastro, N.P. Peet, and P. Bey J. Org. Chem. 54 1989 3913
16. S. Kano, T. Yokomatsu, H. Iwasawa, and S. Shiroshi Chem. Pharm. Bull. 36 1988 3341
17. S. Kano, T. Yokomatsu, H. Iwasawa, and S. Shiroshi Chem. Pharm. Bull. 36 1988 3296
18. J. Liu, N. Ikemoto, D. Petrillo, and J.D. Armstrong Tetrahedron Lett. 43 2002 8223
19. A. Boudier, L.O. Bromm, M. Lotz, and P. Knochel Angew. Chem., Int. Ed. 39 2000 4414
20. P. Knochel, W. Dohle, N. Gommermann, F.K. Florian, F. Kopp, T. Korn, I. Sapountzis, and V.A. Vu Angew. Chem., Int. Ed. 42 2003 4302
21. K. Oshima, A. Inoue, K. Kitagawa, and H. Shinokubo J. Org. Chem. 66 2001 4333
22. M. Schlosser, G. Katsoulos, and S. Takagishi Synlett 1991 731
23. R. Tillyer, L.F. Frey, D.M. Tschaen, and U.-H. Dolling Synlett 1996 225
24. M.J. Williams, R.B. Jobson, N. Yasuda, G. Marchesini, U.-H. Dolling, and E.J.J. Grabowski Tetrahedron Lett. 36 1995 5461
25. S. Sengupta, S. Mondal, and D. Das Tetrahedron Lett. 40 1999 4107
26. f < 500 ppm). The solution was cooled using an acetone/dry ice bath (2 precipitates out of solution at -10°C), and i-PrMgCl in THF (40 ml, 2 M, 80 mmol) was slowly added to the reaction so that the internal temperature ≤-5°C. At the end of the addition, the external cooling was removed, and the reaction was aged at ambient temperature overnight (reaction usually completes within 6 h). HCl (5 N, 23 ml) was charged to a separate vessel and cooled to 0°C, and the reaction mixture was then charged so that the internal temperature was ≤5°C. MTBE (20 ml) was added, mixed, and the layers separated. The pH of the aqueous layer was 4.1 (typical range 3.7-4.4). The MTBE layer was then washed with water (20 ml) and saturated aq NaCl (20 ml), and then concentrated via vacuum distillation to approximately 20 ml at 26-28 in. Hg and internal temperature of 25-30°C. Heptane (100 ml) was added, and the solution was distilled to 65 ml, with the internal temperature 45-60°C and 26-28 in. Hg. The solution was slowly cooled to 35°C, and then seeded (approx. 1 wt %). The slurry was then slowly cooled to 10°C over 2.5 h. The solids were filtered, washed with 20 ml cold heptane, and the cake was dried on the filter, 69% isolated yield, >99% ee. The experimental procedure as described for 1 through the satd aq NaCl wash was used for the remainder of the examples. The MTBE was then evaporated and the residue chromatographed on silica gel, eluting with hexanes/ethyl acetate. The purified product was then used as a standard to determine reaction yield by HPLC.