Optimization of solid-phase syntheses via on-line spectroscopic monitoring

Conventional solution-phase chemical synthesis involves a number of discrete synthetic steps from which intermediates and products are isolated for characterization at the completion of each step. In solid-phase synthesis, intermediates are linked to a solid support and are not removed until the product is isolated at synthesis completion. This approach facilitates the removal of unwanted by-products and maximizes yield. Solid-phase synthetic procedures typically suffer from a number of drawbacks including the use of large excesses of reagents to drive reactions to completion, long reaction times, and large volumes of solvent washes required to remove unreacted reagents between steps. This work describes the use of spectroscopic techniques to optimize solid phase synthesis by making measurements in both the solid and liquid phases. These measurements can lead to faster processing times, reduced chemical waste, and a reduction in the amount of reagents used.