Diethyl Ether → Methyl 4-{[(tert-butoxy)carbonyl]amino}bicyclo[2.2.1]heptane-1-carboxylate

Participants

Reaction Steps

To a solution of 4-(methoxycarbonyl)bicyclo[2.2.1]heptane-1-carboxylic acid (2.01 g, 10.1 mmol) in toluene (30 mL) was added diphenyl phosphoryl azide (2.20 mL, 10.2 mmol) and TEA (1.60 mL, 11.5 mmol). The mixture was stirred at room temperature for about 1 h followed by heating at about 50° C. for about 3 h and further heating at about 70° C. for about 2 h. The reaction was cooled to room temperature and concentrated to dryness under reduced pressure. The residue was diluted in tert-butanol (10.0 mL, 105 mmol) and the mixture was heated at about 80° C. for about 16 h. The reaction mixture was cooled to room temperature and dissolved in Et2O (50 mL). The organic layer was washed with water, aqueous 1 M NaOH, water, and brine (25 mL each). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated to provide methyl 4-(tert-butoxycarbonylamino)bicyclo[2.2.1]heptane-1-carboxylate as an off-white solid (2.22 g, 81%): 1H NMR (400 MHz, DMSO-d6) δ 7.03 (s, 1H), 3.59 (s, 3H), 1.95-1.74 (m, 6H), 1.60 (s, 4H), 1.37 (s, 9H).

Provenance & Evidence