A short and efficient synthesis of (R,R)-2-methylcyclopropanecarboxylic acid

Organic Process Research and Development

Volumn 11, Issue 4, 2007, Pages 689-692

  Delhaye, Laurent ^a   Merschaert, Alain ^a,b   Delbeke, Pieter ^a   Briône, Willy ^a  

^a Eli Lilly Benelux   (Belgium)

^b UCB PHARMA   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 34547881071     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op060249m     Document Type: Article

References (23)

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13. (a) See ref 1.
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15. Under our optimal conditions (HexLi/MeTHF/150 °C), a pressure of 10 bar is obtained with a reactor filled at one-third of its volume. The use of t-BuONa at 110 °C allows lowering the pressure at 4 to 5 bar.
16. Low conversions in hydrocarbons were attributed to the formation of very thick slurries resulting in bad mixing.
17. 1H NMR on isolated material. The differences typically observed (∼5%) were attributed to the volatility of 2a.
18. GC- and LC-MS analyses on isolated 2a indicated the possible formation of di- and oligomers from byproducts 3, 4, and 5. Traces of tert-butyl ester were also detected.
19. Bp = 50 °C/40 mbar.
20. MeTHF solubility in water at 20 °C = 14 g/100 g; water solubility in MeTHF at 20 °C = 4 g/100 g. For a study of MeTHF as efficient process solvent, see: Aycock, D. F. Org. Process Res. Dev. 2007, 11, 156.
21. 1H NMR spectra and GC chromatograms as Supporting Information).
22. Bergman, R. G. J. Am. Chem. Soc. 1969, 91, 7405.
23. Safety studies (adiabatic T° rise calculation and VSP) have been performed before moving forward with the scaleup (6.25 kg). Details are included as Supporting Information