Acetaldehyde → HCID 75480808, compound

To a 250-mL 3-neck flask was added a THF solution (20 mL) of 2-bromo-5-fluoropyridine (8.80 g, 50 mmol). At −78° C., to the solution was added LDA (25.0 mL, 50 mmol, 2.5 M in THF) dropwise. After stirring for 5 min, diisopropylamine (7.0 mL, 50 mmol) was added dropwise via a syringe and the mixture was stirred at −78° C. for 4 h. A THF solution of acetaldehyde (11 mL, 55 mmol, 5M in THF) was added dropwise via a syringe. The contents were removed from the cold bath and stirred with warming to room temperature overnight. The mixture was diluted with water (150 mL) and vigorously stirred for 5 min. The contents were concentrated under reduced pressure and the residue was extracted with ethyl ether (3×150 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure to afford yellow oil, which was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (10:1 to 5:1) to afford 325b (8.0 g, 72.7%) as a yellow solid. MS-ESI: [M+H]+ 220.1. 1H NMR (500 MHz, CDCl3) δ 8.15 (d, J=1.5 Hz, 1H), 7.68 (d, J=5.5 Hz, 1H), 5.17 (d, J=6.5 Hz, 1H), 2.18-2.16 (m, 1H), 1.52 (d, J=6.5 Hz, 3H).

1. stirringthe mixture was stirred at −78° C. for 4 h
2. customThe contents were removed from the cold bath
3. stirringstirred
4. additionThe mixture was diluted with water (150 mL)
5. stirringvigorously stirred for 5 min
6. concentrationThe contents were concentrated under reduced pressure
7. extractionthe residue was extracted with ethyl ether (3×150 mL)
8. dry with materialThe combined organic layer was dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto afford yellow oil, which
12. customwas purified by silica-gel column chromatography
13. washeluting with petroleum ether/ethyl acetate (10:1 to 5:1)

ORD record

ord-76e949db90934c22931fc50da587b543

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716274B2