5-BROMO-2-CHLORO-PYRIDIN-3-OL

Yellow solid

The product from Example 40A (9.8 g, 56.3 mmol) and NaOH (2.40 g, 100 mmol) in water (100 mL) were treated with NaOCl (35 ml of 10percent solution). The reaction mixture was stirred at ambient temperature for 16 hours and then quenched with acetic acid (5 ml), extracted with ethyl acetate (500 mL), dried (MgSO4), and concentrated under reduced pressure. The residue was purified on SiO2 (3percent MeOH/CH2Cl2) to provide the title compound (11.20 g, 96percent yield) as a yellow solid. MS (DCI/NH3) m/z 208, 210 (M+H)+.The product from Example 23A (9.8 g, 56.3 mmol) and NaOH (2.40 g, 100 mmol) in water (100 mL) were treated with aqueous NaOCl (35 mL of 10percent solution). After stirring at ambient temperature for 16 hours, the mixture was quenched with acetic acid (5 ml) and then extracted with ethyl acetate (500 mL). The organic phase was dried (MgSO4) and concentrated. The residue was purified on SiO2 (dichloromethane:methanol, 97:3) to provide the title compound as a yellow solid (11.20 g, 96percent). MS (DCI/NH3) m/z 208/210 (M+H)+.Dissolve NaOH (4 g, 100 mmol) in water (100 mL).3-Bromo-5-hydroxypyridine (9.8 g, 56.3 mmol) was slowly added at 0°C.Then, NaClO (10percent aqueous solution, 35 mL) was slowly added, and the mixture was stirred at room temperature overnight. Acetic acid was added until the pH of the mixture was about 7, the aqueous phase was extracted with ethyl acetate (100 mL×3), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by flash column chromatography (petroleum ether/acetic acid) Ester = 1 : 1) Compound 52-d (7 g, 60percent) was obtained.To a solution of NaOH (2.40 g, 1 15 mmol) in water (96mL) was added 5- bromopyridin-3-ol (10. Og, 57.5 mmol), followed by NaOCI aq. solution (60 ml of 10percent solution). The reaction mixture was stirred at rt for 16 hours and then quenched with acetic acid (7 ml). The precipitate was isolated by filtration and washed with water (200 mL). After drying under high vacuum, 7.0 g of product was obtained (59percent). A solution of 3-(benzyloxy)-5-bromo-2-chloropyridine 4 (4.8 g, 16.08 mmol) in a mixture of AcOH (55 mL) and 40percent HBr (14 mL) was refluxed for 1 h 30 min. The reaction mixture was cooled to room temperature and was slowly poured into saturated aqueous solution of sodium carbonate. The resulting precipitate was collected by filtration and washed with cold water. The solid was dissolved in ethyl acetate, dried over sodium sulfate, and concentrated to dryness. The resulting oil was purified by column chromatography eluting with an 8/2 mixture of petroleum ether and diethyl ether to afford 5 (3.05 g, 91percent) as a white solid. Mp 182-183 °C; IR (KBr): 3448, 1558, 1411, 1173 cmExample 12B EXAMPLE 10B A mixture of 5-bromo-2-chloro-3-methoxypyridine (36 g 162 mmol) in hydrobromic acid (200 mL 3683 mmol) was stirred at 100 for 48 hrs. Then the mixture was concentrated basified with saturated NaHCO