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

Temperature

-20 °C

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:

1. temperaturewas maintained at this temperature for 15 min
2. additionwas added dropwise
3. temperaturewhile maintaining the temperature below -65° C
4. customdid not rise above -60° C
5. stirringAfter stirring at -78° C. for 1 h
6. temperatureto warm to -30° C.
7. temperaturemaintained at this temperature for 30 min
8. temperaturecooled below 0° C
9. customThe aqueous layer was separated
10. washwashed with ether (3×20 ml)
11. extractionAfter extraction with chloroform (3×25 ml) the combined organic extracts
12. dry with materialwere dried over sodium sulphate
13. concentrationconcentrated in vacuo

ORD record

ord-d6b603be1310461d8608a4c64f867a20

Source dataset

uspto-grants-1994_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05324724