反应详情

To a solution of 6′-bromo-4-methoxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (3) (923 mg, 2.99 mmol) and 2-methylpropane-2-sulfinamide (1.450 g, 11.96 mmol, 4 eq.) in anhydrous THF (75 mL) was added Ti(OEt)4 (5.46 g, 4.96 mL, 23.92 mmol, 8.0 eq). The resulting mixture was heated to reflux overnight. LC-MS showed ca. 45% conversion. After another 8 h, no further improvement. To the refluxing mixture was added 2-methylpropane-2-sulfinamide (0.725 g, 5.98 mmol, 2 eq.) and Ti(OEt)4 (2.73 g, 2.5 mL, 11.96 mmol, 4.0 eq) and followed by another equal portions of 2-methylpropane-2-sulfinamide and Ti(OEt)4 after 14 hours. The reaction mixture was refluxed for another 2 days, 93% conversion achieved at this point. The reaction was quenched with brine (3 mL) after cooled down to room temperature. The mixture was stirred for another 30 min before filtered through a short pad of Celite®. The filter cake was washed with EA, and the filtrate was concentrated to dryness. The residue was purified by silica gel chromatography. The fraction of desired product with 2-methylpropane-2-sulfinamide was dissolved in EA (100 mL) and washed with saturated aqueous NaHCO3 (45 mL), 1 M NaOH (40 mL) and brine successively. Solvent was removed under reduced pressure after dried over Na2SO4 and filtered to afford 0.968 g of the desired product 4 as a light yellow solid. MS ESI+ve m/z 412 (M+H)+.

1. temperatureThe resulting mixture was heated
2. temperatureto reflux overnight
3. temperatureThe reaction mixture was refluxed for another 2 days
4. customThe reaction was quenched with brine (3 mL)
5. filtrationbefore filtered through a short pad of Celite®
6. washThe filter cake was washed with EA
7. concentrationthe filtrate was concentrated to dryness
8. customThe residue was purified by silica gel chromatography
9. dissolutionThe fraction of desired product with 2-methylpropane-2-sulfinamide was dissolved in EA (100 mL)
10. washwashed with saturated aqueous NaHCO3 (45 mL), 1 M NaOH (40 mL) and brine successively
11. customSolvent was removed under reduced pressure
12. dry with materialafter dried over Na2SO4
13. filtrationfiltered