Installation of the acrylamide warhead was low-yielding in the initial developments. Minor refinements lead to substantial gains, however (Figure ). Use of the sodium salt of 2-fluoroacrylic acid promoted both acylation activity and stability of the starting material and eliminated need for external base (Et3N). This greatly improved yield to 89% AY and 70% IY. The majority of material loss occurred during two crystallizations which were conducted to ensure exceptional purity of the final API.