Dimethyl Sulfoxide → 4,6-Dichloro-2-methylnicotinaldehyde

Temperature

-78 °C

A dry flask was charged with DCM (59.9 mL) and oxalyl chloride (3.15 mL, 35.9 mmol) and cooled to −78° C. Dimethyl sulfoxide (3.40 mL, 47.9 mmol) was added and the reaction was stirred for 30 min. A solution of (4,6-dichloro-2-methylpyridin-3-yl)methanol (4.60 g, 23.95 mmol) in DCM (2 mL) was then added. The reaction was stirred for 30 min then triethylamine (6.74 mL, 71.9 mmol) was added and the reaction mixture was stirred at −78° C. for 30 min. The reaction was warmed to 0° C. and stirred for 1 h. The reaction was then quenched with sodium bicarbonate, diluted with water, and the aqueous layer extracted with EtOAc. The organic phase was washed with sat. sodium bicarbonate, dried over MgSO4, filtered, and concentrated in vacuo to afford 4,6-dichloro-2-methylnicotinaldehyde, which was carried onto the next step without further purification. 1H NMR (500 MHz, DMSO-d6) δ 10.60 (s, 1H), 7.37 (s, 1H), 2.80 (s, 3H).

1. stirringThe reaction was stirred for 30 min
2. stirringthe reaction mixture was stirred at −78° C. for 30 min
3. temperatureThe reaction was warmed to 0° C.
4. stirringstirred for 1 h
5. customThe reaction was then quenched with sodium bicarbonate
6. additiondiluted with water
7. extractionthe aqueous layer extracted with EtOAc
8. washThe organic phase was washed with sat. sodium bicarbonate
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-35d701dac31e4d2b96e08252367ec44d

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233979B2