A simple, modular method for the synthesis of 3,4,5-trisubstituted pyrazoles

Journal of Organic Chemistry

Volumn 73, Issue 11, 2008, Pages 4309-4312

  McLaughlin, Mark ^a   Marcantonio, Karen ^a   Chen, G Yi ^a   Davies, Ian W ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATOMIC PHYSICS; ATOMS; CARBON; CHEMICAL REACTIONS; COMPUTER NETWORKS; ESTERS; ORGANIC COMPOUNDS; SYNTHESIS (CHEMICAL);

(I ,J) CONDITIONS; AMERICAN CHEMICAL SOCIETY (ACS); BORONIC ESTERS; CARBON ATOMS; CHEMICAL EQUATIONS; DEBORONATION; LITHIATION; MODULAR APPROACH; NON-AQUEOUS; PYRAZOLE; PYRAZOLE RINGS; PYRAZOLES; SUZUKI CROSS COUPLINGS; SWITCHABLE; SYNTHESIS (OF CHIRAL IONIC LIQUIDS);

NUMERICAL METHODS;

PYRAZOLE DERIVATIVE;

ARTICLE; CHEMICAL ANALYSIS; CHEMICAL MODIFICATION; CHEMICAL REACTION; CHEMICAL STRUCTURE; SUZUKI REACTION; SYNTHESIS;

MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; PYRAZOLES; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION;

EID: 44949111442     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo800321p     Document Type: Article

References (18)

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15. Important modifications to the existing literature procedure that are relevant to larger-scale operation of this chemistry include reduced excess of DHP (1.05 vs 1.5 equiv) and controlled addition of this reagent at 80°C to avoid a serious exotherm observed using an "all-in" mode (see Supporting Information for further details). Distillative workup was also eliminated. For further details regarding the kinetic profile of this reaction, see: Schafer, W. A.; Hobbs, S.; Rehm, J.; Rakestraw, D. A.; Orella, C.; McLaughlin, M.; Ge, Z.; Welch, C. J. Org. Process Res. Dev. 2007, 11, 870-876.
16. Proteolytic deboronation of heterocyclic substrates can be problematic and was observed by Prof. Fu when employing a pyrazole-4-boronic acid substrate (ref 6).
17. Alternatively, the THP-pyrazoles are stable to chromatography and can be isolated (pure) using this technique.
18. Ethyl ester 7e suffered double addition of n-BuLi leading to a tertiary alcohol.