A pilot-scale synthesis of (1R)-trans-2-(2,3-dihydro-4-benzofuranyl) cyclopropanecarboxylic acid: A practical application of asymmetric cyclopropanation using a styrene as a limiting reagent

Tetrahedron Asymmetry

Volumn 14, Issue 22, 2003, Pages 3569-3574

  Simpson, James H ^a   Godfrey, Jollie ^a   Fox, Rita ^a   Kotnis, Atul ^a   Kacsur, David ^a   Hamm, Jason ^a   Totelben, Michael ^a   Rosso, Victor ^a   Mueller, Richard ^a   Delaney, Edward ^a   Deshpande, Rajendra P ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (2,3 DIHYDRO 4 BENZOFURANYL)CYCLOPROPANECARBOXYLIC ACID; CYCLOPROPANECARBOXYLIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CRYSTALLIZATION; CYCLOPROPANATION; DIASTEREOISOMER; DRUG HYDROLYSIS; DRUG PURIFICATION; DRUG SYNTHESIS; ENANTIOSELECTIVITY; PRIORITY JOURNAL;

EID: 0242541869     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetasy.2003.08.041     Document Type: Article

References (16)

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2. Some previous examples where olefin was used as a limiting reagent, see: (a) Doyle, M. P.; Van Leusen, D.; Tamblyn, W. H. Synthesis 1981, 787-789; (b) Majchrzak, M. W.; Kotelko, A. Synthesis 1983, 469-470.
3. Ellis, F.; Panchal, T.; North, P.; Cooke, J.; Smith, C. (Glaxo Wellcome) W00743272 A2 19971120.
4. Rao M., Yang M., Kuehner D., Grosso J., Deshpande R.P. Org. Proc. Res. Develop. 7:2003;547-550.
5. For recent reviews, see: (a) Pfalz, A.; Lydone, K.; McKervey, M. A.; Charette, A. B.; Leel, H. In Comprehensive Asymmetric Catalysis; Jacobsen E. N. ; Pfalz, A.; Yamamoto, H., Eds.; Springer, 1999; pp. 513-603; (b) Doyle, M. P.; Protopopova, M. Tetrahedron 1998, 54, 7919-7946; (c) Doyle, M. P.; Forbes, D. C. Chem. Rev. 1998, 98, 911-935.
6. Evans D.A., Woerpel K.A., Hinman M.M., Faul M.M. J. Am. Chem. Soc. 113:1991;726-728.
7. Fukuda T., Katsuki T. Tetrahedron. 53:1997;7201-7208.
8. Nishiyama H., Itoh Y., Sugawara Y., Matsumoto H., Aoki K., Itoh K. Bull. Chem. Soc. Jpn. 68:1995;1247-1262.
9. 4-Vinyl-2,3-dihydrobenzofuran was prepared to according to the procedure described in Ref. 3. The authors would like to thank Dr. Meena Rao and Ms. Ming Yang for providing several laboratory scale batches of the vinyl- dihydrobenzofuran for the evaluation of the cyclopropanation.
10. Nishiyama H., Yamaguchi S., Kondo M., Itoh K. J. Org. Chem. 57:1992;5814.
11. 4-1 consisting of 8 factorial points plus 4 center points to measure experimental error. This experiment was able to examine main effects on reaction completion, and confounded 2-way interactions between four factors such as concentration of olefin, equiv. of diazoacetate, concentration of diazoacetate and addition rate of diazoacetate.
12. Kotnis, A. S.; Simpson, J. H.; Deshpande, R. P.; Kacsur, D. J.; Hamm, J. ; Kodersha, G.; Merkl, W.; Domina, D.; Wang, S. S. Y. Org. Proc. Res. Develop., in press.
13. Totleben M.J., Prasad J.S., Simpson J.H., Chan S.H., Vanyo D.J., Kuehner D.E., Deshpande R., Kodersha G.A. J. Org. Chem. 66:2001;1057-1060.
14. Initially, the diastereoselective crystallization using (+)-dehydroabeitylamine was developed by our colleague Dr. Brian Kaller for the resolution of racemic 2. During this development 26 homochiral amines under various solvent conditions were evaluated prior to selection of (+)-dehydroabeitylamine.
15. In the pilot plant, the dehydroabeitylamine salt 5 was not dried due to dust hazards associated with it. Although the salt was found to be thermally stable, it was electrically non-conductive and was highly sensitive to electrical ignition. Therefore, after MTBE washes, the salt was washed with water, centrifuged and isolated as ca. 50 wt% water wet material. Authors would like to thank D. Domina and W. Merkl and Dr. S. Wang for providing safety assessment on the salt and the New Brunswick Pilot Plant staff for successful scale-up operations.
16. Takeda, N.; Ishii, S.; Sumitomo Chemicals Co.; Ltd. Patent JP48103514, 12/25/93. CA.: 80:132837.