Hydrochloric Acid → 3-(5-Pyrimidinyl)-1-azabicyclo[2.2.2]octan-3-ol

Participants

Reaction Conditions

Reaction Steps

n-Butyllithium (12 ml of a 1.6M solution in hexane 19.2 mmol), at -110° C., was added dropwise to a solution of 5-bromopyrimidine (2.0 g, 12.5 mmol) in THF (60 ml) and ether (60 ml), at -110° C. (ethanol/liquid nitrogen bath). The resultant yellow solution was stirred at -110° C. for 1.25 h and a solution of quinuclidinone (1.72 g, 13.75 mmol) in THF (20 ml) also at -110° C., added dropwise. The reaction mixture was stirred at -110° C. for 0.1 h then warmed to room temperature and stirred for 16 h. 2N-Hydrochloric acid (25 ml) was added and stirred for 0.25 h. The organic phase was washed with water (15 ml) and the combined aqueous extracts basified with potassium carbonate and extracted with dichloromethane (4×75 ml). Chromatography of the residue obtained upon removal of the solvents through alumina using dichloromethane/methanol (90:10) as eluant, gave 3-(5-pyrimidinyl)-1-azabicyclo[2.2.2]octan-3-ol as a yellow solid, m.p. 126°-127° C. (ethyl acetate/ether); (Found C,61.42; H,7.47; N,19.60. C11H15N3O. O.5H2O requires C,61.66; H,7.53; N,19.61%); m/e 205(M+); δ (360 MHz,D2O) 1.30-1.44(1H,m,0.5×CH2); 1.65-1.74(2H,m,CH2); 2.10-2.20(1H,m,0.5×CH2); 2.30-2.32(1H,m,CH-bridgehead); 2.68-2.96(4H,m,2×CH2); 3.09(1H,dd,J=1.5 and 14.7 Hz, 0.5×CH2); 3.49(1H,dd,J=1.5 and 14.7 Hz,0,5×CH2); 8.96(2H,s,pyrimidine-H); 9.08(1H,s,pyrimidine-H).

Provenance & Evidence