Scale-up of a Reformatsky reaction to an indenyl butanoate

Organic Process Research and Development

Volumn 9, Issue 2, 2005, Pages 216-218

  Scherkenbeck, Thomas ^a   Siegel, Konrad ^a  

^a BAYER PHARMA AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

5 METHOXY 1 INDANONE; BUTYRIC ACID; BUTYRIC ACID DERIVATIVE; INDANONE DERIVATIVE; INDENYL BUTANOATE; METHYL 2 BROMOBUTYRATE; UNCLASSIFIED DRUG;

ARTICLE; LABORATORY; REACTION ANALYSIS; REFORMATSKY REACTION; SAFETY; SCALE UP;

EID: 17444403989     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op049778l     Document Type: Article

References (19)

1. Zhang, M.; Zhu, L.; Ma, X Tetrahedron: Asymm. 2003, 14, 3447-3453.
2. (a) Reformatsky, S. Ber. Dtsch. Chem. Ges. 1887, 20, 1210-1211.
3. (b) for a recent review: Ocampo, R.; Dolbier, W. R., Jr. Tetrahedron 2004, 60, 9325-9374.
4. (a) Erdik, E. Tetrahedron 1987, 43, 2203-2212.
5. (b) Newman, M. S. J. Am. Chem. Soc. 1942, 64, 2131-2133.
6. (c) Gawronsky, J. K. Tetrahedron Lett. 1984, 25, 2605-2608.
7. (d) Knochel, P.; Normant, J. F. Tetrahedron Lett. 1984, 25, 1475-1478.
8. Reformatsky reaction on pilot-plant scale has been used in: (a) Clark, J. D.; Weisenburger, G. A.; Anderson, D. K.; Colson, P.-J.; Edney, A. D.; Gallagher, D. J.; Kleine, H. P.; Knable, C. M.; Lantz, M. K.; Moore, M. V.; Murphy, J. B.; Rogers, T. E.; Ruminski, P. G.; Shah, A. S.; Storer N.; Wise, B. E. Org. Process Res. Dev. 2004, 8, 51-61. (b) Atkins, R. J.; Breen, G. F.; Crawford, L. P.; Grinter, T. J.; Harris, M. A.; Hayes, J. F.; Moores, C. J.; Saunders: R. N.; Share A. C.; Walsgrove T. C.; Wicks, C. J. Org. Process Res. Dev. 1997, 1, 185-197.
9. Reformatsky reaction on pilot-plant scale has been used in: (a) Clark, J. D.; Weisenburger, G. A.; Anderson, D. K.; Colson, P.-J.; Edney, A. D.; Gallagher, D. J.; Kleine, H. P.; Knable, C. M.; Lantz, M. K.; Moore, M. V.; Murphy, J. B.; Rogers, T. E.; Ruminski, P. G.; Shah, A. S.; Storer N.; Wise, B. E. Org. Process Res. Dev. 2004, 8, 51-61. (b) Atkins, R. J.; Breen, G. F.; Crawford, L. P.; Grinter, T. J.; Harris, M. A.; Hayes, J. F.; Moores, C. J.; Saunders: R. N.; Share A. C.; Walsgrove T. C.; Wicks, C. J. Org. Process Res. Dev. 1997, 1, 185-197.
10. Basu, B.; Maity, S. K.; Mukherjee, D. Synth. Commun. 1981, 11, 803-809.
11. Oda, Y.; Matsuo, S.; Saito K. Tetrahedron Lett. 1992, 33, 97-100.
12. The induction period and the necessary amount of bromoester 3 needed For initiation of the reaction varied between experiments. No correlation to any reaction parameter (such as concentration or addition rate) could be observed.
13. (a) For a use of Zn-Cu couple in a Reformatsky reaction see: Santaniello, E.; Manzocchi A. Synthesis 1977, 698-699.
14. (b) We prepared the Zn-Cu couple according to McMurry, J. E.; Lectka, T.; Rico, J. G. J. Org. Chem. 1989, 54, 3748-3749.
15. No other acids were tried for the activation of the Zn metal in situ.
16. adj = 33 K.
17. Addition of 3 at 20°C failed to initiate the reaction; 45°C was chosen as a compromise of safety and reliability.
18. adj = 36 K.
19. 4 as estimated by mass balance. The contamination of Zn ions in the aqueous waste was not investigated.