Pentane → 6-(Methylsulfanyl)-1H-indole

Temperature

0 °C

A mixture of potassium hydride in mineral oil (35 wt. %, 3.04 g, 26.52 mmol) in tetrahydrofuran (53 mL) was cooled to 0° C. then was treated with a solution of 6-bromo-1H-indole (5.20 g, 26.52 mmol) in tetrahydrofuran (53 mL). The reaction was stirred at 0° C. for 30 min. At this time, the reaction was cooled to −78° C. and then was treated with 1.7M solution of tert-butyllithium in pentane (31.2 mL, 53.04 mmol). The reaction mixture was stirred at −78° C. for 20 min. At this time, the reaction was added to a solution of methyl disulfide (4.78 mL, 53.04 mmol) in tetrahydrofuran (15 mL). The reaction was then allowed to warm to 25° C. where it was stirred for 18 h. At this time, the reaction was quenched by the addition of a saturated aqueous ammonium chloride solution (300 mL) and was extracted with ethyl acetate (1×500 mL). The organic layer was washed with a saturated aqueous sodium chloride solution (1×300 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 9:1 hexanes/ethyl acetate) afforded 6-methylsulfanyl-1H-indole (2.3 g, 53%) as an off-white solid: mp 88-90° C.; EI-HRMS m/e calcd for C9H9N5 (M+) 163.0456, found 163.0457.

1. temperatureAt this time, the reaction was cooled to −78° C.
2. stirringThe reaction mixture was stirred at −78° C. for 20 min
3. temperatureto warm to 25° C. where it
4. stirringwas stirred for 18 h
5. customAt this time, the reaction was quenched by the addition of a saturated aqueous ammonium chloride solution (300 mL)
6. extractionwas extracted with ethyl acetate (1×500 mL)
7. washThe organic layer was washed with a saturated aqueous sodium chloride solution (1×300 mL)
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-efbaa56cc156447693d490a71b67fedf

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881844B2