A practical non-cryogenic process for the selective functionalization of bromoaryls

Tetrahedron Letters

Volumn 49, Issue 34, 2008, Pages 5024-5027

  Gallou, Fabrice ^a   Haenggi, Ruedi ^a   Hirt, Hans ^a   Marterer, Wolfgang ^a   Schaefer, Frank ^a   Seeger Weibel, Manuela ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Bromine magnesium exchange; Magnesiate; Non cryogenic; Selective

Indexed keywords

BROMINE DERIVATIVE; LITHIUM; MAGNESIUM DERIVATIVE; REAGENT;

ARTICLE; CHEMICAL REACTION; CROSS COUPLING REACTION; SAFETY; SYNTHESIS;

EID: 46749151287     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2008.06.046     Document Type: Article

References (50)

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50. General procedure: To a solution of aryl bromide (12 mmol, 1.2 equiv) in dry THF (12 mL) at 0 °C was added a 2 M solution of iPrMgCl in THF (5 mmol, 0.5 equiv) in 5 min. The clear solution was stirred at that temperature for an additional 10 min, and a 30% solution of nBuLi in hexanes(10 mmol, 1.0 equiv) was added dropwise in 10 min, while maintaining the temperature below 5 °C. The resulting mixture was stirred at that temperature for 1 h, cooled to -10 °C, and dry DMF (13 mmol, 1.3 equiv) in dry THF (13 mL) was added dropwise in 10 min. The resulting mixture was warmed to rt in 1 h, and added to a 0.5 M citric acid solution at rt. After 10 min stirring, the phases were separated and the water phase was extracted one additional time with toluene. The combined organic phases were concentrated and water was removed azeotropically with toluene to obtain the desired aldehyde. All benzaldehyde products were compared to commercially available reference samples.