Dimethylformamide → 3-Formyl-4-methoxypyridine

Temperature

-78 °C

A flask is charged with 1.7M tert-butyllithium in pentane (47.1 mL, 80.1 mmol) and THF (20 mL), and cooled to −78° C. 2-Bromomesitylene (6.0 mL, 39 mmol) is added dropwise. The mixture is stirred for 1 h, and 4-methoxypyridine (3.0 mL, 30 mmol) is added dropwise. The mixture is warmed to −23° C. and stirred for 3 h. The mixture is cooled again to −78° C. and dimethylformamide (3.5 mL, 45 mmol) is added. After 1 h, brine (50 mL) is added to the mixture at −78° C. and warmed to room temperature. The mixture is extracted with ether and the combined organic layer is dried over Na2SO4. Concentration followed by silica gel chromatography eluting with a 0 to 6% methanol-dichloromethane gradient gives 4-methoxy-pyridine-3-carbaldehyde. 1H NMR (400 MHz, CDCl3) δ ppm 4.01 (s, 3H), 6.94 (d, J=5.8 Hz, 1H), 8.65 (d, J=5.8 Hz, 1H), 8.90 (s, 1H), 10.46 (s, 1H).

1. temperatureThe mixture is warmed to −23° C.
2. stirringstirred for 3 h
3. temperatureThe mixture is cooled again to −78° C.
4. waitAfter 1 h
5. temperaturewarmed to room temperature
6. extractionThe mixture is extracted with ether
7. dry with materialthe combined organic layer is dried over Na2SO4
8. concentrationConcentration
9. washeluting with a 0 to 6% methanol-dichloromethane gradient

ORD record

ord-7229f37b78f14526a099db346d8881bc

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242963B2