Methanesulfonyl chloride → 2-Bromo-5-(methylsulfonyl)pyridine

Temperature

0 °C

To a solution of 2,5-dibromopyridine (50 g, 211 mmol) in tetrahydrofuran (175 mL) at 0° C. was added 2.0 M isopropylmagnesium chloride (274 mmol) at a rate which maintained the temperature below 8° C. The reaction mixture was stirred at 0° C. for 45 minutes, then cooled to −15° C. A solution of methanesulfonyl chloride (32.2 g, 281 mmol) in tetrahydrofuran (40 mL) was added to the reaction mixture at a rate which maintained the temperature below 5° C. The reaction mixture was allowed to warm to room temperature and then quenched with water (500 mL) and tert-butylethylether (300 mL). The layers were separated, the aqueous layer was extracted twice with tert-butylethylether (2×200 mL). The combined organic extracts were washed with water (200 mL) and concentrated. The crude product was crystallized from toluene (110 mL) and the solids were filtered to afford 29.4 g (59% yield) of 2-bromo-5-(methanesulfonyl)-pyridine. Analytical data: 1H NMR (300 MHz, CDCl3) δ 3.13 (s, 3H), 7.73 (d, J=8.3 Hz, 1H), 8.07 (dd, J1=8.3 Hz, J2=2.7 Hz, 1H), 8.91 (d, J=2.5 Hz, 1H).

1. temperaturemaintained the temperature below 8° C
2. temperaturecooled to −15° C
3. temperaturemaintained the temperature below 5° C
4. temperatureto warm to room temperature
5. customquenched with water (500 mL) and tert-butylethylether (300 mL)
6. customThe layers were separated
7. extractionthe aqueous layer was extracted twice with tert-butylethylether (2×200 mL)
8. washThe combined organic extracts were washed with water (200 mL)
9. concentrationconcentrated
10. customThe crude product was crystallized from toluene (110 mL)
11. filtrationthe solids were filtered

ORD record

ord-a2e63f6868c146dfb4ae299a6a8092ea

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06646128B2