Sodium Methoxide → (R)-N-{4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]pyrimidin-2-yl}quinuclidine-3-amine

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Reaction Steps

A 5 L 3-neck round bottom flask is charged with the N-1-azabicyclo[2.2.2]oct-3-ylguanidine hydrochloride (261.5 g, 1.277 mol) and absolute ethanol. Sodium methoxide (21% by weight) (405 ml, 1.08 mol) is added dropwise over 15 min. The 3-(dimethylamino)-1-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]prop-2-en-1-one (232.1 g, 0.776 mol) is then added in portions so that no reaction mixture temperature change is observed. The reaction mixture is then refluxed for 5 hours and cooled to room temperature. Solvent is removed in vacuo and the residue partitioned between 1N NaOH and ethyl acetate. The resulting solids are filtered, washed with water, ethyl acetate, and then dried. The solids are then mostly dissolved in hot isopropyl alcohol and filtered through celite while hot. The isopropyl alcohol solution is concentrated to dryness and the solids dried under vacuum to give the desired pyrimidine compound (143.8 g) as a tan solid in 46% yield.

Provenance & Evidence