1,8-Diazabicyclo(5.4.0)undec-7-ene → tert-butyl 3-(cyanomethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate

Participants

Reaction Steps

In a 5 L flask, tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (Preparation F, Step A; 94.2 g, 485 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (85.6 g, 441 mmol) were dissolved in acetonitrile (882 mL). To this was then added DBU (33.0 mL, 220 mmol). The resulting clear orange brown mixture was stirred at ambient temperature for 15 hours. The reaction mixture was concentrated down to remove solvents and afforded a dark reddish-orange oil. Solid crystals formed within a few hours at ambient temperature. This was isolated by washing with cold Et2O and cold EtOAc (carefully to prevent dissolution) to afford 110 g (64% yield) of the title compound. The recrystallization was repeated to give another 13.7 g (8% yield). Additional compound was isolated by purification of the filtrate from the above recrystallization. This was purified by silica chromatography eluting with a 20-50% EtOAc/Hexanes gradient to afford an additional 22.7 g (13%) of the title compound. MS (apci) m/z=289.2 (M+H-Boc).

Provenance & Evidence