Dimethyl Disulfide → HCID 22988007, compound

Temperature

-78 °C

2,2,6,6-Tetramethylpiperidine (1.76 ml, 10.40 mmol) was dissolved in tetrahydrofuran (39 ml) and placed under an atmosphere of nitrogen. The solution was cooled to −78° C. and n-butyllithium (3.96 ml, 9.91 mmol, 2.5 M solution of in hexanes) was added at such a rate that the internal temperature did not exceed −70° C. The reaction mixture was warmed to −10° C. for 30 min., then re-cooled to −78° C. A solution of 1-tert-butoxycarbonyl-3-(4-fluorophenyl)-2-(pyridin-4-yl)-pyrrolo[3,2-b]pyridine (0.965g, 2.47 mmol) in tetrahydrofuran (32 ml) was cooled to −78° C. and then added via cannula at such a rate that the internal temperature did not exceed −70+ C. After 1 h, dimethyldisulfide (0.29 ml, 3.22 mmol) was added and the resulting solution was stirred for an additional 1 h at −78° C. The reaction mixture was quenched with saturated ammonium chloride solution and the product was extracted into ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The crude residue was purified by flash chromatography using 20% acetone/hexanes as the eluant to give 1-tert-butoxycarbonyl-3-(4-fluorophenyl)-7-methylthio-2-(pyridin-4-yl)-pyrrolo[3,2-b]pyridine. MS: 435 (M).

1. customdid not exceed −70° C
2. temperatureThe reaction mixture was warmed to −10° C. for 30 min.
3. temperaturere-cooled to −78° C
4. additionadded via cannula at such a rate that the internal temperature
5. customThe reaction mixture was quenched with saturated ammonium chloride solution
6. extractionthe product was extracted into ethyl acetate
7. washThe organic layer was washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated in vacuo
10. customThe crude residue was purified by flash chromatography

ORD record

ord-b642486c44064a5a825328adc5a405d3

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06316464B1