Hydrogen Peroxide → HCID 58388209, compound

Temperature

-78 °C

Under a nitrogen atmosphere and with stirring, a sample of 30 (50 mg, 0.176 mmol) was suspended in dry THF (1.4 mL) and the solution was cooled to −78° C. in a dry ice/isopropanol bath. To the stirred mixture was added lithium diisopropylamide (LDA, 2 M in THF/n-heptane/ethylbenzene, 132 μL, 0.26 mmol) dropwise. The isopropanol bath was then removed and the mixture was allowed to reach room temperature over 20 minutes. The mixture was again cooled to −78° C. and to it was added dropwise a solution of phenylselenenyl chloride (66.5 mg, 0.347 mmol, 2 eq) in dry THF (0.42 mL). The isopropanol bath was removed and the reaction was stirred at room temperature for 2 hours. During this time a yellow precipitate appeared, indicating the formation of solid lithium chloride. The reaction was then quenched with brine (5 mL) and the aqueous layer was extracted with dichloromethane/ethyl ether (1:2, 3×4 mL). The organic layers were combined, washed with brine (1×4 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to give a dark yellow-brown residue. This residue was dissolved in ethyl ether (2.82 mL) and hydrogen peroxide (30% aqueous, 3×42.3 μL) was added in 3 successive portions, allowing the mixture to stir 5 minutes between each addition. After the third portion was added, the color of the mixture changed from brown to pale yellow and translucent. The reaction mixture was then washed with water (1×4 mL), saturated aqueous sodium bicarbonate solution (2×4 mL), and brine (1×4 mL). The organic layers were combined and dried over magnesium sulfate, filtered, and concentrated in vacuo to give the crude product as a yellow oil (43.1 mg). The crude was purified by flash column chromatography [hexanes-ethyl acetate (5:1)] to give 31 (19.2 mg, 0.068 mmol, 39%) as a clear oil: 1H NMR (CDCl3) δ 7.34-7.24 (5H, m), 6.74 (1H, dd, J=1.5, 10 Hz), 5.94 (1H, dd, J=0.6, 10 Hz), 2.98 (1H, d, J=13 Hz), 2.89 (1H, d, J=13 Hz), 2.46 (2H, dt, J=5, 17 Hz), 2.08 (2H, td, J=1.5, 6 Hz), 0.16 (9H, s); 13C NMR (CDCl3) δ 209.1, 199.1, 152.1, 135.9, 130.9, 128.2, 128.1, 127.3, 109.0, 106.1, 89.4, 46.4, 38.5, 35.0, 34.5, 0.11; MS (ESI+) m/z 283.1 [M+H]+, HRMS (ESI+) calcd for C18H22OSi+H 283.1518. found 283.1508.

1. customThe isopropanol bath was then removed
2. temperatureThe mixture was again cooled to −78° C. and to it
3. customThe isopropanol bath was removed
4. stirringthe reaction was stirred at room temperature for 2 hours
5. customThe reaction was then quenched with brine (5 mL)
6. extractionthe aqueous layer was extracted with dichloromethane/ethyl ether (1:2, 3×4 mL)
7. washwashed with brine (1×4 mL)
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give a dark yellow-brown residue
12. stirringto stir 5 minutes between each addition
13. additionAfter the third portion was added
14. washThe reaction mixture was then washed with water (1×4 mL), saturated aqueous sodium bicarbonate solution (2×4 mL), and brine (1×4 mL)
15. dry with materialdried over magnesium sulfate
16. filtrationfiltered
17. concentrationconcentrated in vacuo
18. customto give the crude product as a yellow oil (43.1 mg)
19. customThe crude was purified by flash column chromatography [hexanes-ethyl acetate (5:1)]

ORD record

ord-2b830877a38b46ad9ef1c9521bb4fac5

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09000188B2