Reaction Steps
A solution of (R)—N-(quinoxalin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (190 mg, 0.614 mmol) and 3-chlorobenzoperoxoic acid (165 mg, 0.737 mmol) in 4 mL THF was stirred at room temperature for 2 h. The reaction was concentrated and the crude product was purified by flash chromatography on a 40 g silica gel cartridge with 1 to 30% [9:1 MeOH/NH4OH] in EtOAc. Pure fractions were pooled, concentrated, redissolved in CHCl3, and filtered through a 0.45 u filter to yield (S)-2-(quinoxalin-2-ylamino)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octane]1′-oxide (192 mg, 96% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.89 (1H, br. s.), 8.58 (1H, s), 7.93 (1H, dd, J=8.31, 1.26 Hz), 7.70 (1H, dd, J=8.31, 1.01 Hz), 7.60 (1H, ddd, J=8.25, 6.99, 1.38 Hz), 7.50 (1H, ddd, J=8.25, 6.99, 1.38 Hz), 4.01 (1H, d, J=10.07 Hz), 3.84 (1H, d, J=9.82 Hz), 3.78-3.83 (1H, m), 3.64 (1H, dd, J=14.35, 2.27 Hz), 3.26-3.58 (4H, m), 2.50-2.65 (1H, m), 2.27 (1H, br. s.), 2.06-2.19 (1H, m, J=14.26, 10.42, 4.15, 4.15 Hz), 1.88-2.03 (2H, m). LCMS: RT=0.72 min, MH+=326.1 [ Waters Acquity SDS: 2 to 98% B, 1 min gradient; hold 98% B, 0.5 min; flow rate 0.8 mL/min; Solvent A: 100% H2O/0.05% TFA; Solvent B: 100% ACN/0.05% TFA]. LCMS: RT=1.15 min, MH-=324.2, MH+=326.2 [ Phenomenex LUNA C18 3 m (2.0×30 mm); 0 to 100% B, 2 min gradient; flow rate 1 mL/min; Solvent A: 5% MeOH: 95% water: 10 mM NH4OAc; Solvent B: 95% MeOH: 5% water: 10 mM NH4OAc; 220 nM].
