Phosphoric Acid → (+/-) 1(1-Azabicyclo [2.2.2]oct-3-yl)-2-(phenylsulphinyl) ethanone

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of n-butyllithium (2.7 ml of a 1.6M solution in hexanes, 4.3 mmol) in dry tetrahydrofuran (5 ml) cooled to -78° C. under nitrogen was added dropwise a solution of diisopropylamine (0.44 g, 4.3 mmol) in dry tetrahydrofuran (5 ml). The mixture was allowed to warm to -20° C., and was maintained at this temperature for 15 min. After cooling to -78° C. a solution of methyl phenyl sulphoxide (0.55 g, 3.9 mmol) in dry tetrahydrofuran (2 ml) was added dropwise while maintaining the temperature below -65° C. The reaction was stirred for a further 5 rain and then a solution of (±) 1-azabicyclo[2.2.2] oct-3-yl-N-methyl-N-methoxycarboxamide (EP 322182, Description 22) (0.65 g, 3.3 mmol) in dry tetrahydrofuran (5 ml) was added rapidly while ensuring that the temperature did not rise above -60° C. After stirring at -78° C. for 1 h, the reaction was allowed to warm to -30° C., and maintained at this temperature for 30 min. The reaction was then poured into vigorously stirred orthophosphoric acid (20ml of a 5% H3PO4 solution) cooled below 0° C. The aqueous layer was separated, washed with ether (3×20 ml) and then saturated with potassium carbonate. After extraction with chloroform (3×25 ml) the combined organic extracts were dried over sodium sulphate and concentrated in vacuo to give the title compound (D1) as an oil (1.0 g) consisting of a 1:1 mixture of diastereomeric keto sulphoxides. 1H NMR (CDCl3) δ:

Provenance & Evidence