Microwave-assisted organic synthesis optimization

In this chapter we discuss the new speeding-up techniques, optimized during the last decade, such as solid-phase extraction, polymer-assisted solution-phase synthesis, microwave-assisted organic synthesis, and flow chemistry. The improvements obtained with these techniques are not limited to a subset of chemical reactions (e.g., the reported examples), but they are fully applicable to the entire set of chemistry involved in the synthetic drug discovery process. 

Combs P, Takvorian AG (2004) Microwave-assisted organic synthesis using minivials to optimize and expedite the synthesis of diverse purine libraries. J Comb Chem 6 171-174... 

This timescale of these microwave-assisted reactions is in minutes and it enables a facile and rapid scoping of reaction conditions, for example, time, temperature, reagents and solvents. This rapid optimization can be used to rapidly identify routes for the synthesis of novel chemical entities. Microwave-assisted organic synthesis is no longer a curiosity now, it is a rapidly growing technology, but it has not been used with full potential. 

Whereas in the last decade microwave irradiation was mainly applied to accelerate and optimize well-known and established reactions, current trends are indicative of the future use of microwave technology for the development of completely new reaction pathways in organic synthesis. Limited by vessel and cavity size, microwave-assisted synthesis has hitherto been focused predominantly on reaction optimiza-... 

Microwave acceleration of reactions is a valuable tool for organic synthesis [39], and various specialized instruments are now commercially available. Tye and co-workers have reported the microwave-assisted Petasis borono-Mannich reaction of arylboron-ic acids and primary or secondary amines with either glyoxylic acid or salicylaldehyde [40]. Optimized reaction conditions employed didiloromethane as solvent, and microwave assisted heating at 120 °C for 10 min. Products were obtained in generally modest yields (10-83%), in part due to incomplete reaction conversion imder the reported conditions. 

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