2-Fluoro-1,3-dimethylimidazolidin-1-ium hexafluorophosphate(V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dried flask was charged with 1.00 g (3 mmol) of (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (Intermediate 3) and 865 mg (3.3 mmol) of 2-fluoro-1,3-dimethylimidazolidinium hexafluorophosphate, followed by 7.5 mL of anhydrous DMF. The resulting solution was stirred under nitrogen gas with cooling in an ice bath as 0.835 mL of triethylamine was added by syringe through a septum, and this was followed by 0.291 mL (300 mg, 6 mmol) of hydrazine hydrate. After several min, the ice bath was removed, and the mixture was allowed to warm to room temperature. After 1 h, 40 mL of water was added very gradually by syringe, accompanied by vigorous stirring. This resulted in precipitation of product. One hour later, the solid was collected on a filter, washed generously with water, and dried. The crude product was dissolved in dichloromethane-methanol and evaporated onto several grams of silica gel, which was loaded onto the top of a silica gel column. Flash chromatography (1-4% methanol in dichloromethane) provided the title compound as a white solid, mp 168-168.5° C. LC-MS 248 (M+1-Boc). was added by syringe through a septum After several min, the ice bath was removed 40 mL of water was added very gradually by syringe This resulted in precipitation of product One hour later, the solid was collected on a filter washed generously with water dried The crude product was dissolved in dichloromethane-methanol evaporated onto several grams of silica gel, which