Practical synthesis of (1 s,4 s)-4-(methylamino)-1′ H-spiro[cyclohexane-1,3′-furo[3,4-c]pyridin]-1′-one

Organic Process Research and Development

Volumn 14, Issue 5, 2010, Pages 1269-1271

  Bish, Gerwyn ^a   De Koning, Pieter D ^a   Dubant, Stephané P A ^a   Fengas, David ^a   Fray, M Jonathan ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BUILDING BLOCKES; CHEMICAL PURITY; DIASTEREOMERS; FUNCTIONALIZED; PHARMACEUTICAL RESEARCH; STEP SEQUENCES;

CYCLOHEXANE;

EID: 77956917854     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op100138t     Document Type: Article

References (11)

1. Maeda, K.; Kato, S.; Iida, T.; Tschaen, D. M. Process for Making Spirolactone Compounds. U.S. Patent 2003/0144515 A1, 2003.
2. Fukami, T.; Kanatani, A.; Ishihara, A.; Ishii, Y.; Takahashi, T.; Haga, Y.; Sakamoto, T.; Itoh, T. Spiro Compounds. U.S. Patent 6,803,372, 2002.
3. Urban, F. J.; Anderson, B. G.; Stewart, M. A.; Young, G. R. Org. Process Res. Dev. 1999, 3, 460
4. Fichtner, M. W. Private communication.
5. Iida, T.; Satoh, H.; Maeda, K.; Yamamoto, Y.; Asakawa, K.; Sawada, N.; Wada, T.; Kadowaki, C.; Itoh, T.; Mase, T.; Weissman, S. A.; Tschaen, D.; Krska, S.; Volante, R. P. J. Org. Chem. 2005, 70, 9222
6. Boy, K. M.; Dee, M.; Yevich, J.; Torrente, J.; Gao, Q.; Iben, L.; Stark, A.; Mattson, R. J. Bioorg. Med. Chem. Lett. 2004, 14, 4467
7. In addition to the desired products (2a / 2b), other metal catalysts (e.g., nickel and platinum) also gave varying amounts of the alcohol derived from ketone reduction and in general gave much less pure product. The diastereomeric ratio (2a / 2b) was fairly consistent for all the hydrogenation methods examined. Since methylamine is conveniently available as a 33 wt % solution in ethanol, this was the solvent of choice. Methylamine in THF was also screened but afforded a poor reaction profile and was not investigated further.
8. For a recent publication of a related reductive amination where co-ordination to a Lewis acid was found to influence the diastereoselectivity, see: Allmendinger, S.; Gallou, F.; Han, B.; Lu, J.; Seeger-Weibel, M.; Stoessel, A.-F. Tetrahedron Lett. 2010, 51, 1419
9. The reaction was stopped after consumption of 1 equiv of hydrogen. In our experience there was no obvious change in hydrogen uptake rate after this point, and reactions that were left for extended periods contained significant quantities of over-reduced material. Using a less active hydrogenation catalyst was also beneficial in reducing the level of over-reduction.
10. In addition to those listed in Table 1, the following acids were screened: acetic, benzoic, (d)-di- O, O ′-benzoyl- d -tartaric acid, dl -camphorsulfonic, citric, formic, HBr, HCl, 1-hydroxy-2-naphthoic, dl -lactic, l -malic, methanesulfonic, phosphoric, succinic, sulfuric, d -tartaric, (d)-di- O, O ′- p -toluoyl- d -tartaric acid.
11. Park, Y.-T.; Jung, C.-H.; Kim, K.-W.; Kim, H. S. J. Org. Chem. 1999, 64, 8546