1-Hydroxybenzotriazole → (1S,6R)-tert-Butyl 8-(2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoyl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate

Participants

Reaction Steps

To a solution of 3,8-diaza-bicyclo[4.2.0]octane-3-carboxylic acid tert-butyl ester (550 mg, 2.59 mmol) in CH2Cl2 (9 mL) was added 2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid (545 mg, 2.59 mmol) followed by EDCl (745 mg, 3.89 mmol), HOBt (525 mg, 3.89 mmol) and TEA (0.72 mL, 5.18 mmol). The mixture was stirred for 14 h at room temperature and then washed (2×) with saturated aqueous NH4Cl solution. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Chromatography (Hex to 100% EtOAc/Hex) afforded the desired product as a colorless foam (665 mg, 61%). MS (ESI): mass calculated for C21H26N4O4, 398.20, m/z found 399.0 [M+1]+. 1H NMR (500 MHz, CDCl3): 8.14-8.05 (m, 1H), 7.67-7.52 (m, 2H), 7.45-7.36 (m, 1H), 4.39-4.21 (m, 2H), 4.04-3.96 (m, 1H), 3.90-3.83 (m, 0H), 3.77-3.43 (m, 3H), 2.96-2.76 (m, 2H), 2.47 (s, 3H), 2.03-1.72 (m, 2H), 1.54-1.36 (m, 9H).

Provenance & Evidence