Pyridine → 4-Phenylbicyclo[2.2.2]oct-1-ylmethyl toluene-4-sulfonate

Temperatur

2.5 °C

Pyridine (4 mL), then a solution of toluene-4-sulfonyl chloride (7.4 g, 38.81 mmol) in dry DCM (30 mL), were added to a stirred solution of (4-phenylbicyclo[2.2.2]oct-1-yl)methanol (7.0 g, 32.36 mmol) in DCM (70 mL), maintaining 0-5° C. throughout. The reaction mixture was stirred at 0° C. overnight, refluxed for 2 h then cooled to 35° C. Further pyridine (2 mL) and a solution of toluene-4-sulfonyl chloride (3.9 g) in DCM (10 mL) were added and the mixture stirred at reflux for 2 h. As some starting material remained, a catalytic amount of 4-dimethylaminopyridine was added and the mixture stirred under reflux overnight. The mixture was cooled, diluted with DCM (200 mL) then washed with water (100 mL), hydrochloric acid (2M; 150 mL), water (50 mL), sat. aq. NaHCO3 (100 mL), water (50 mL) and brine (50 mL). After drying (MgSO4) the solution was concentrated to give crude product which was purified by silica column chromatography (silica 40-63 micron) eluting with hexane:ethyl acetate (19:1 to 4:1) to afford the title compound as a pale yellow solid (10.7 g, 89%).

1. temperaturerefluxed for 2 h
2. temperaturethen cooled to 35° C
3. stirringthe mixture stirred
4. temperatureat reflux for 2 h
5. stirringthe mixture stirred
6. temperatureunder reflux overnight
7. temperatureThe mixture was cooled
8. washthen washed with water (100 mL), hydrochloric acid (2M; 150 mL), water (50 mL), sat. aq. NaHCO3 (100 mL), water (50 mL) and brine (50 mL)
9. dry with materialAfter drying (MgSO4) the solution
10. concentrationwas concentrated
11. customto give crude product which
12. customwas purified by silica column chromatography (silica 40-63 micron)
13. washeluting with hexane:ethyl acetate (19:1 to 4:1)

ORD-Eintrag

ord-dc873e5d2d104c9ba718de4863790f26

Quelldatensatz

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07749997B2