5-bromo-2-phenoxypyridine

General procedure: 2, 4-Dibromopyridine (0.236 g, 1 mmol) and phenol (0.094 g, 1 mmol), CuI (19.0 mg, 0.1 mmol), TMEDA (11.6 mg, 0.1 mmol), and cesium carbonate (0.65 g, 2 mmol) were placed in DMSO (5 mL). The reaction was stirred at 110 °C under nitrogen atmosphere for 24 h. When the reaction mixture was cooled, the reaction mixture was filtered. The mixture was dissolved with dichloromethane (25 mL). Then the mixture was washed with brine (3×30 mL). The organic phase was dried over sodium sulfate. After evaporation of the solvent, the mixture was subjected to column chromatography with petroleum ether/ethyl acetate (20:1) as eluent to give pure product.General procedure: Procedure (take intermediate 3a as an example): 2, 5-dibromopyridine (61.5 mmol), phenol (64.6 mmol), cuprous iodide (6.15 mmol), and Cs2CO3 (92 mmol) were placed in a 250 mL dried flask. Add 150 mL DMSO, then add TMEDA (6.15 mmol), heated to 110 degrees under Ar protection (Unless otherwise specified, the temperature in the present invention is in degrees Celsius °C), react for about 20 hours, TLC conversion complete. After cooling to room temperature, a large amount of ethyl acetate was added, the mixture was washed 4 times with water and extracted twice with ethyl acetate. The combined EA (ethyl acetate) phase was washed with brine, and the organic layer was dried, filtered and evaporated to dryness to give the product as a brown oil.A mixture of 2, 5-dibromopyridine (237mg, 1 mmol , 1.0 eq), phenol (140mg, 1.5 mmol , 1.5eq), Cu (32.5 mg, 0.5 mmol , 0.5eq), CuT (95 mg , 0.5 mmol , 0.5eq) and Cs2CO3 (978 mg, 3.0 mmol, 3.Oeq) in NMP (10 mL) was heated to 135 °C for 5 h under N2. The solid was filtered off and the filtrate was concentrated and purified by column chromatography(EA/PE=10/1, vlv) to provide 5-bromo-2- phenoxypyridine as a brown solid (200 mg, 84.4percent).In a 100-liter reactor, Phenol (0.94 kg, 10 mol) was added successively, Dimethylformamide (20 kg), 2, 5-dibromopyridine (2.37 kg, 10 mol)Anhydrous sodium carbonate (1.27 kg, 12 mol), The reaction mixture was heated to 105 ° C by jacket and the reaction was stirred for 24 hours.To be 2, 5-dibromopyridine consumption is complete, The reaction was cooled to room temperature, discharged, and filtered.The filtrate is returned to the reactionKettle and cooled to 0 ° C by jacket, Stirring was added in portions (40 kg)Control the temperature of 5-8 , 0.5 hours plus finished, Precipitation of light yellow solid, The mixture was stirred at this temperature for 2 hours, discharged, and filtered.The filter cake was washed with ice water (10 kg) and then filtered to dryness, The filter cake was dissolved in n-heptane (10 kg)The insoluble matter was removed by suction filtration, and the resulting filtrate was concentrated to dryness, and dimethylformamide (8 kg) was added to dissolve, The solution was cooled to 0 ° C and crushed ice (10 kg) was added over a period of 1 hour at a temperature of 3-5 ° C, Precipitation of solid, stirring 2 hours aging, suction filtration, The filter cake was washed with ice water (10 kg)Drain dry yellow solid 2.05kg, Yield: 82percent, purity: 95.4percent.Manufacturing Example 40-1-1 5-Bromo-2-phenoxy-pyridine; To a solution of phenol (1.97 g, 20.9 mmol) in N, N-dimethylformamide (100 mL) was added sodium hydride (1.00 g, 20.9 mmol) at 0° C., which was stirred for 5 minutes at 0° C. 2, 5-Dibromopyridine (4.50 g, 19.0 mmol) was then added to this reaction solution at 0° C., and stirred for 40 minutes at room temperature. The reaction solution was then stirred for further 3 hours at 120° C. After allowing to room temperature, the reaction solution was partitioned into water and ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=6:1) to obtain the title compound (3.85 g, 81percent).To a solution of phenol (1.97 g, 20.9 mmol) in N, N-dimethylformamide (100 mL) was added sodium hydride (1.00 g, 20.9 mmol) at 0° C., which was stirred for 5 minutes at 0° C. 2, 5-Dibromopyridine (4.50 g, 19.0 mmol) was then added to this reaction solution at 0° C., and stirred for 40 minutes at room temperature. The reaction solution was then stirred for further 3 hours at 120° C. After allowing to room temperature, the reaction solution was partitioned into water and ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=6:1) to obtain the title compound (3.85 g, 81percent). To a suspension of NaH (203 mg, 5.06 mmol) in DMF (15 mL), at 0 °C and under NGeneral procedure: To a solution of alcohol 1a-r or benzyl mercaptan 1s (1.5 equiv.) in anhydrous THF (100 mL) was slowly added 60percent sodium hydride (2.0 equiv.). The mixture was allowed to react at room temperature for 30 min then it was heated to reflux for 1 h. 5-bromo-2-fluoropyridine (1 equiv.) was added and the reaction was continued for 12 h. After cooling down to room temperature, the mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with brine, dried on MgSO

Molecular Weight:250.09
XLogP3:3.1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:248.97893
Monoisotopic Mass:248.97893
Topological Polar Surface Area:22.1
Heavy Atom Count:14
Complexity:171
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes