Dimethylformamide → 3-Fluoro-2-pyridinecarboxaldehyde

Temperature

-20 °C

Dry ethyl ether (500 mL), n-BuLi (1.6M in hexane, 62.5 mL, 0.1 mol), and dry 1,4-diazabicyclo[2.2.2]octane (DABCO) (11.56 g, 0.1 mol) were introduced into a 1 L flask under a dry N2 stream at -60° C. and the resulting cloudy solution was stirred for 1 hour at -20° C. The mixture was then cooled to -75° C. and an ethyl ether (50 mL) solution of 3-fluoropyridine (9.81 g, 0.1 mol) was added dropwise and stirring continued for 1 1/2 hours at -60° C. The mixture was recooled to -75° C., dry N,N-dimethylformamide (8.52 mL, 0.11 mol) dissolved in ethyl ether (50 mL) was added dropwise and the mixture stirred for 2 hours at -75° C. Water (175 mL) was introduced slowly at -10° C., the aqueous layer extracted with ethyl acetate (5×200 mL), and the combined extracts were dried over anhydrous sodium sulfate. Solvent removal produced a dark brown oil which after vacuum distillation and purification by chromatography on silica gel provided 4.4 g (35%) of the titled product as an off-white crystalline solid:

1. customstream at -60° C.
2. temperatureThe mixture was then cooled to -75° C.
3. stirringstirring
4. customcontinued for 1 1/2 hours at -60° C
5. customwas recooled to -75° C.
6. additionwas added dropwise
7. stirringthe mixture stirred for 2 hours at -75° C
8. extractionthe aqueous layer extracted with ethyl acetate (5×200 mL)
9. dry with materialthe combined extracts were dried over anhydrous sodium sulfate
10. customSolvent removal
11. customproduced a dark brown oil which
12. distillationafter vacuum distillation and purification by chromatography on silica gel

ORD record

ord-17d376bce16d41ac90ed1aef70f170fd

Source dataset

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05714503