6-Bromo-2-fluoro-3-hydroxypyridine

To a stirred solution of 2-fluoropyridin-3-ol (J. Labelled Cou7npound. Radioplzann., 1998, 41, 451) (3.81 g, 33.7 mmol) and sodium acetate (2.76 g, 33.7 mmol) in acetic acid (30 mL) was added bromine (1.74 mL, 33.7 mmol) at 0°C, and the mixture was stirred at room temperature for 3.5 hours. The mixture was poured onto ice-aq. sodium hydroxide and extracted with ethyl acetate. The combined organic layer was dried and evaporated to afford the titled compound as a yellow solid (4.67 g, 72 percent). 'H NMR (270MHz, DMSO-d6) 8 = 7.29 (d, J = 8.2 Hz, 1H), 7.28 (s, 1H), 7.23 (d, J = 8.2 Hz, 1H) ppm. MS (EI) ; M+=191, 1936-f2-r4-(6-fluoro-5-methoxypyridin-2-yl)-4-hydroxypiperidin-1-, yll-1- hydroxyethyl}-3, 4-dihydroquinolin-2(1H)-one hydrochloride; A. 6-bromo-2-fluoropyridin-3-ol; To a stirred solution of 2-fluoropyridin-3-ol (J. Labelled Coumpound. Radiophann., 1998, 41, 451) (3.81 g, 33.7 mmol) and sodium acetate (2.76 g, 33.7 mmol) in acetic acid (30 mL) was added bromine (1.74 mL, 33.7 mmol) at 0 °C, and the mixture was stirred at room temperature for 3.5 hours. The mixture was poured onto ice-aq. sodium hydroxide and extracted with ethyl acetate. The combined organic layer was dried and evaporated to afford the titled compound as a yellow solid (4.67 g, 72 percent). 'H NMR (270MHz, DMSO-d6) 8 = 7.29 (d, J = 8.2 Hz, 1H), 7.28 (s, 1H), 7.23 (d, J = 8.2 Hz, 1H) ppm. MS (EI) ; M+=191, 193To a stirring solution of 2-fluoropyridin-3-ol (8.00 g, 70.7 mmol) in acetic acid (70 mL), potassium acetate (4.25 g, 70.7 mmol) was added. The solution was cooled to 0 °C after the potassium acetate had dissolved. Bromine (3.65 mL, 70.7 mmol) in acetic acid (10 mL) was added dropwise and the resulting mixture was stirred at room temperature for 1 h. Sodium sulfite (5 g) was added, followed by 1 N NaOH (30 mL). After the brown color of the solution disappeared, the solution was extracted with EtOAc (2 x 100 mL). The EtOAc extracts were combined, washed with water (100 mL), saturated NaHC0A stirred solution of 2-fluoro-3-pyridinol (1.10 g, 9.73 mmol) and NaOAc (0.80 g, 9.73 mmol) in HOAc (10 mL) was treated with BrStep-1: Preparation of 6-bromo-2-fluoropyridin-3-ol [0175] To a solution of 2-fluoropyridin-3-ol (1 g, 8.842 mmol) and sodium acetate (0.72 g, 8.842 mmol) in acetic acid (10 mL) was added bromine (0.23 mL, 8.842 mmol) at 0 °C and the reaction mixture was stirred at room temperature for 4 h. The solution was poured into ice, pH was adjusted to 6 using 2N sodium hydroxide solution and extracted with ethyl acetate (50 mL x 2). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to afford the crude product, which was purified by silica gel column chromatography (10percent ethyl acetate/hexane) to obtain the title compound 6-bromo-2- fluoropyridin-3-ol (0.5 g, 30percent yield) as a colorless liquid. Calculated (M+H): 193; Found (M+l): 193.9Step-1: Preparation of 6-bronio-2-fluoropyridin-3-ol [00130] To a solution of 2-fluoropyridin-3-ol (1 g, 8.842 mmol) and sodium acetate (0.72 g, 8.842 mmol) in acetic acid (10 mL) was added bromine (0.23 mL, 8.842 mmol) at 0 °C and the reaction mixture was stirred at room temperature for 4 h. The solution was poured into ice, pH was adjusted to 6 using 2N sodium hydroxide solution and extracted with ethyl acetate (50 mL x 2). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to afford the crude product, which was purified by silica gel column chromatography (10percent ethyl acetate/hexane) to obtain the title compound 6-bromo-2- fluoropyridin-3-ol (0.5 g, 30percent yield) as a colorless liquid. Calculated (M+H): 193; Found (M+l): 193.9

Molecular Weight:191.99
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:190.93820
Monoisotopic Mass:190.93820
Topological Polar Surface Area:33.1
Heavy Atom Count:9
Complexity:103
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes