4-Acetylpyridine → HCID 71544292, compound

Temperature

0 °C

To a stirred solution of DIPA (0.13 mL, 0.00092 mmol) in THF (7 mL) at −78° C. was added n-BuLi (0.76 mL, 0.001226 mmol). The mixture was allowed to stir at 0° C. for 30 min, was again cooled to −78° C., and then a solution of 2-(4-fluorophenyl)oxazole (0.1 g, 0.000613 mmol) in THF (2 mL) was added dropwise during 30 min. 4-Acetyl pyridine (0.07 mL, 0.000674 mmol) in THF (2 mL) was then added, the reaction mixture was stirred for an additional 1 hour at −78° C., quenched with saturated ammonium chloride (2 mL), diluted with water (10 mL), and extracted with ethyl acetate (20 mL). The organic layer was dried with sodium sulfate, filtered and the solvent was concentrated under reduced pressure to obtain crude product. The crude product was purified by silica gel chromatography (200-400 mesh, 2% of methanol in dichloromethane) to give 1-(2-(4-fluorophenyl)oxazol-5-yl)-1-(pyridin-4-yl)ethanol (0.14 g, 82%) as white solid in 98.5% HPLC purity. 1H NMR (400 MHz, DMSO-d6): δ 8.53 (d, 2H), 7.95-7.91 (m, 2H), 7.45 (d, 2H), 7.32 (t, 2H), 7.14 (d, 1H), 6.38 (s, 1H), 1.81 (s, 3H); LC-MS m/z calculated for [M+H]+ 285.10, found 285.1.

1. temperaturewas again cooled to −78° C.
2. stirringthe reaction mixture was stirred for an additional 1 hour at −78° C.
3. customquenched with saturated ammonium chloride (2 mL)
4. additiondiluted with water (10 mL)
5. extractionextracted with ethyl acetate (20 mL)
6. dry with materialThe organic layer was dried with sodium sulfate
7. filtrationfiltered
8. concentrationthe solvent was concentrated under reduced pressure
9. customto obtain crude product
10. customThe crude product was purified by silica gel chromatography (200-400 mesh, 2% of methanol in dichloromethane)

ORD record

ord-37cac240388843eb99c4cf2c3697cc2c

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809372B2