1,3-Cyclohexadiene → tert-Butyl 2-oxa-3-azabicyclo[2.2.2]oct-5-ene-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

Solid N-hydroxycarbamic acid tert-butyl ester (100.19 g, 752.3 mmol) was added to a slurry of NaIO4 (168.68 g, 788.6 mmol), 1,3-cyclohexadiene (86.0 mL, 902 mmol) and 50% MeOH/CH2Cl2 (3 L) cooled in an ice bath. The ice bath was removed after the addition. After 2 h, a warm (37° C.) water bath was installed for 5 min to raise the temperature from 17° C. to 24° C., at which point the bath was removed. The mixture thickened from a turbid solution to a white slurry, and the temperature climbed over 50 minutes to a peak of 40° C. before dropping slowly. Analysis by TLC (50% EtOAc/hexanes) at the temperature peak indicated the reaction was all but complete, and when it had cooled to room temperature the mixture was filtered and rinsed with EtOAc (3×175 mL). The filtrate was concentrated in vacuo to a cloudy oil which was partitioned between EtOAc (700 mL) and satd NaHSO3 (400 mL). Organic layer was extracted with satd NaHSO3 (200 mL), and the combined aqueous layers were extracted with EtOAc (100 mL). The combined organic layers were washed with H2O (100 mL) and satd NaCl (100 mL), and were then dried (Na2SO4) and concentrated to provide 146.80 g (92%) of amber oil.

Provenance & Evidence