Development of large-scale preparations of indole derivatives: Evaluation of potential thermal hazards and studies of reaction kinetics and mechanisms

Organic Process Research and Development

Volumn 10, Issue 6, 2006, Pages 1178-1183

  Akao, Atsushi ^a   Nonoyama, Nobuaki ^a   Mase, Toshiaki ^a   Yasuda, Nobuyoshi ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33845501190     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op060150f     Document Type: Article

References (26)

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3. Akao, A.; Hiraga, S.; Iida, T.; Kamatani, A.; Kawasaki, M.; Mase, T.; Nemoto, T.; Satake, N.; Weissman, S. A.; Tschaen, D. M.; Rossen, K.; Petrillo, D.; Reamer, R. A.; Volante, R. P. Tetrahedron 2001, 57, 8917.
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7. Metal iron and/or aluminum amalgam reductions are known. However, they usually result in moderate yields and have the disadvantage of requiring labor-intensive workup procedures to remove metal residues. In addition, disposal of the waste metals can become an environmental problem. Therefore, these conditions are suitable for large-scale syntheses. Reductions using iron: (a) Knölker, H.-J.; Hartmann, K. Synlett 1993, 755.
8. (b) Sinhababu, A. K.; Borchardt, R. T. J. Heterocycl. Chem. 1988, 25, 1155.
9. Reductions using aluminum amalgam: Toste, F. D.; Still, I. W. J. Org. Prep. Proced. Int. 1995, 27, 576.
10. Catalytic hydrogenation using common catalysts are known. In general, these reactions result in high yields but can have low chemoselectivity. (a) Tamara, K., Ed. Hannoubetsu Jitsuyou Shokubai; Kagaku Kougyou Sha Inc.: Tokyo, 1970.
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17. +] 240.1025, found 240.1036.
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25. Indole 4 and N-hydroxyindole 11 were exposed to the hydrogenation conditions with no additives. From 4, an 86:14 mixture of 4 and de-benzylated indole 7 was obtained after standing for 1 h. in contrast, from 11, an 87:12:1 mixture of 11:4:7 was obtained after standing for 1 h. Therefore, the reaction rate from 11 to 7 appears to be slow and could be ignored.
26. Authentic indoles were available from Biosynth International, Inc.