反应详情

6′-(3-Fluoropropoxy)-4-hydroxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (Intermediate 21, 0.91 g, 3.11 mmol), 2-methylpropane-2-sulfinamide (0.566 g, 4.67 mmol) and titanium(IV) ethoxide (1.283 mL, 6.23 mmol) were dissolved in 2-Me THF (8 mL) and heated to reflux over a weekend. More 2-methyl-2-propanesulfinamide (0.189 g, 1.56 mmol) and titanium(IV) ethoxide (0.325 mL, 1.56 mmol) were added, and the mixture was refluxed overnight. The reaction was cooled to r.t. EtOAc (50 mL) and water (10 mL) were added under stirring. The mixture were let to stand still for 1 h. The organic phase was collected by filtration, dried, and concentrated. The residue was purified by flash column chromatography using a gradient of 0-40% EtOAc in heptane, to give 0.278 g (23% yield) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.33 (s, 9 H) 1.45-1.54 (m, 4 H) 1.87 (br. s., 1 H) 2.03 (dd, 2 H) 2.14-2.19 (m, 1 H) 2.20-2.25 (m, 1 H) 2.93-3.01 (m, 2 H) 3.71-3.80 (m, 1 H) 4.13-4.18 (m, 2 H) 4.59-4.66 (m, 1 H) 4.69-4.75 (m, 1 H) 7.11 (dd, 1 H) 7.29 (s, 1 H); MS (ES+) m/z 396.11 [M+H]+.

1. temperatureheated
2. temperatureto reflux over a weekend
3. temperaturethe mixture was refluxed overnight
4. filtrationThe organic phase was collected by filtration
5. customdried
6. concentrationconcentrated
7. customThe residue was purified by flash column chromatography