Phenol → HCID 62472276, compound

Temperature

0 °C

To a solution of tributylphosphine (4.57 g, 22.63 mmol) in anhydrous tetrahydrofuran (20 mL) was added diisopropyl azodicarboxylate (4.57 g, 22.63 mmol) at 0° C. The reaction mixture was stirred for 10 minutes at 0° C., then added to a solution of (2-chloropyridin-4-yl)methanol and phenol in anhydrous tetrahydrofuran (50 mL) at 0° C. The reaction mixture was stirred at 0° C. for 20 minutes then at ambient temperature for 16 hours. The reaction was quenched with saturated ammonium chloride solution (10 mL). The solvent was evaporated in vacuo. The residue was diluted with ethyl acetate (350 mL), washed with 1 N sodium hydroxide solution (3×40 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with ethyl acetate/hexane (1/9) to afford 2-chloro-4-(phenoxymethyl)pyridine as a gummy solid in 61% yield (2.34 g): 1H NMR (300 MHz, CDCl3) δ 8.36 (d, J=5.1 Hz, 1H), 7.40 (s, 1H), 7.32-7.24 (m, 3H), 7.01-6.91 (m, 3H), 5.05 (s, 2H); MS (ES+) m/z 220.2 (M+1).

1. stirringThe reaction mixture was stirred at 0° C. for 20 minutes
2. waitat ambient temperature for 16 hours
3. customThe reaction was quenched with saturated ammonium chloride solution (10 mL)
4. customThe solvent was evaporated in vacuo
5. additionThe residue was diluted with ethyl acetate (350 mL)
6. washwashed with 1 N sodium hydroxide solution (3×40 mL)
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by column chromatography
11. washeluted with ethyl acetate/hexane (1/9)

ORD record

ord-1b9b7211ae394657b5d2f5929a500bab

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501746B2