Flow Cells

Microwave chemistry has long been known to accelerate chemical transformations and provide a simple means to access more rigorous reaction conditions. Flow chemistry has demonstrated similar benefits, with the added bonus of being able to increase the reaction scale simply by prolonging the reaction. The combination of the two technologies opens the door to a quick optimization and easy scale-up of virtually unlimited types of chemical transformations. The Discover® SP System provides the means to perform both types of reactions simultaneously or sequentially within the same system. Use of microwave heating allowed access to a temperature of 190 °C, well above the boiling point of acetonitrile. This increased temperature resulted in a pressure of nearly 200 psi during the batch reaction. Despite these forcing conditions, the reaction proved suitable for synthesis in flow, providing a modest increase in yield with a 20-fold increase in scale.

Table 1: Heck Reagents Required

Reagent	Batch	Flow
Iodobenzene	0.101 g	2.02 g
Butyl acrylate	0.127 g	2.54 g
Pd(OAc)2	0.06 mg	1.2 mg
DIPEA	0.096 g	1.92 mg
MeCN	1 mL	20 mL

Table 2: Heck Coupling Conditions

Mode	Temperature	Time	Scale	Isolated Yield
Batch	190 °C	5 minutes	0.5 mmol	89%
Flow	190 °C	30 minutes	10 mmol	91%