Diethyl Ether → 4-isobutyloxybenzyl isocyanate

Participants

Reaction Steps

4-isobutoxyphenylacetic acid (7.6 g, 36.5 mmol) was dissolved in THF (50 mL). Proton Sponge™ (8.2 g, 38 mmol) was added, and the mixture was stirred for 15 min. Diphenylphosphoryl azide (10.6 g, 38 mmol) was added dropwise and the mixture was heated to reflux for 4 h. The mixture was cooled to room temperature and placed in the freezer at −18° C. for 20 h. The resulting white precipitate was vigorously stirred with diethyl ether (250 mL) for 15 min and filtered. The filtrate was evaporated to give crude 4-isobutoxybenzyl isocyanate (1.97 g, 9.6 mmol), which was dissolved in dichloromethane (50 mL) and added to a solution of 50ELH85 (2.91 g, 9.6 mmol) in dichloromethane (50 mL). The reaction mixture was stirred for 20 h and concentrated. The crude product was purified by flash chromatography (0–5% methanol in dichloromethane) to give N-(4-fluorobenzyl)-N-[1-(trifluoroacetyl)piperidin-4-yl]-N′-(4-isobutyloxybenzyl)carbamide (76ELH17, 3.90 g, 91%).

Provenance & Evidence