tert-Butanol → tert-Butyl 3-oxocyclobutylcarbamate

Participants

Reaction Steps

A 22 L three neck flask was charged with 3-oxocyclobutanecarboxylic acid (630 g, 5.52 mol, 1.0 equiv), toluene (12 L), and triethylamine (850 mL, 6.07 mol, 1.1 equiv). The acid dissolved in toluene after the addition of triethylamine. The solution was cooled below 10° C. and diphenylphosphoryl azide (DPPA) (1.32 L, 6.07 mol, 1.1 equiv) was added dropwise over 15 minutes under N2. The solution was then warmed up to RT and stirred overnight. The reaction mixture was then transferred to 22 L separatory funnel, washed with aqueous NaHCO3 (2×4 L), water (4 L), brine (2 L), dried over MgSO4 and filtered. The filtrate was then transferred to a 22 L three neck flask and to it was added tert-butanol (1260 mL, 13.2 mol, 2.4 equiv). The resultant reaction mixture was then heated at reflux overnight. Upon completion, the reaction mixture was cooled to RT and concentrated under reduced pressure. Another 70 g batch was combined prior to the column purification. The crude residue thus obtained was then purified using column chromatography eluting with ethyl acetate/hexanes (25:75 to 40:60) to afford 350 g of tert-butyl (3-oxocyclobutyl)carbamate (30% yield).

Provenance & Evidence