Ethyl formate → 4-Chloropyridine-3-carbaldehyde

Temperature

-78 °C

4-Chloropyridine (3.1 g, 27.3 mmol, after drying over Na2SO4) was extracted from a mixture of 4-chloropyridine hydrochloride in 5% NaHCO3 with methylene chloride, dissolved in THF (50 mL), and cooled to −78° C. under dry nitrogen, followed by addition of LDA (1.5 M in cylclohexane, 18.2 mL). After 4 hours at −78° C., excess ethyl formate was added quickly. After 3 hours at −78° C., the reaction was allowed to warm to ambient temperature overnight. The reaction was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, chromatographed (20% EtOAc in hexanes), and dried under high vacuum to give 1.47 g of the aldehyde. MS m/e 142 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 7.44 (d, 1H, J=6 Hz), 8.69 (d, 1H, J=6 Hz), 9.06 (s, 1H), 10.51 (s, 1H).

1. waitAfter 3 hours at −78° C.
2. temperatureto warm to ambient temperature overnight
3. extractionextracted with EtOAc
4. washThe combined organic extracts were washed with brine
5. dry with materialdried over Na2SO4
6. customchromatographed (20% EtOAc in hexanes)
7. customdried under high vacuum

ORD record

ord-6a782ea16a894b6eb23cfaa5d4d48cf3

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06693123B2