Methyl p-toluenesulfonate → (+/-)-alpha-(Methoxyimino)-alpha-(1-azabicyclo[3.2.1]oct-2-en-3-yl)acetonitrile

Participants

Reaction Steps

Potassium tert-butoxide (0.807 g, 7.19 mmol) was added portionwise to a solution of (±)3-cyanomethylene-1-azabicyclo[3.2.1]octane (D11) (0.967 g, 6.53 mmol) in THF (40 ml) at -70° C. The resulting solution was stirred for 0.5h at -60° C., then tert-butyl nitrite (0.87 ml of approximately 90% purity, 6.58 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 1.5h. Methyl p-toluenesulphonate (1.215 g, 6.53 mmol) in THF (10 ml) was added dropwise and the resulting mixture was stirred at room temperature overnight, then poured into saturated aqueous potassium carbonate (75 ml) and extracted with ethyl acetate (3×100 ml). The combined organic extracts were dried (Na2SO4) and evaporated to a gum which was subjected to column chromatography on silica in a gradient of 1-5% methanol in chloroform to afford in order of elution (±)-α-(methoxyimino)-α-(1 -azabicyclo[3.2.1]oct-2-en-3-yl)acetonitrile (0.683 g, 55%) as a crystallising oil and (±)-α-(methoxyimino)-α-(1-azabicyclo[3.2.1]oct-3-en-3-yl)acetonitrile (0.194 g, 16%) as an oil. The latter compound was converted to the oxalate salt and recrystallised from acetone/methanol to give the title compound (E6) as a white crystalline solid m.p. 196°-198° C.

Provenance & Evidence