3-Hydroxypyridine → HCID 10255652, compound

Participants

Reaction Conditions

Reaction Steps

To a 50 mL round bottom flask fitted with a magnetic stirrer bar and rubber septum was added 20 mL anhydrous THF (Aldrich) and 2,4-bis(methyl-sulfonyl)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine (Reference Example 5) (1.0 g, 2 mmol). The flask was flushed with nitrogen and cooled to 0° C. In a separate flask, also fitted with a magnetic stirrer bar and rubber septum, was added 10 mL anhydrous THF and 3-hydroxypyridine (213 mg, 2.24 mmol), This flask was flushed with nitrogen and cooled to 0° C. Then n-butyl lithium (1.12 mL, 2.24 mmol) (Aldrich-2M solution in hexane) was added via syringe and the solution stirred for several minutes. The lithium alkoxide solution was then withdrawn by syringe and slowly added to the first reaction flask. The solution was stirred at 0° C. for 1 h, quenched with saturated sodium bicarbonate and the reaction products extracted with ethyl acetate. The organic layer was dried over anhydrous MgSO4, filtered and the solvent removed under reduced pressure. Flash column chromatography on silica gel (eluted with 35/65 hexanes/ethyl acetate) afforded 2-methylsulfonyl-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine: 1H-NMR 500 MHz (CDCl3): δ 3.20 (s, 3H), 7.20-7.25 (m, 4H), 7.30-7.38 (m, 3H), 7.41 (m, 1H), 7.63-7.65 (m, 1H), 8.53-8.55 (m, 2H).

Provenance & Evidence