3-Fluoro-4-methylphenol

Preparation of 3-fluoro-4-methylphenol: 3-Fluoro-4-methylaniline (5g, 39.95 lmmol) was dissolved in 10percent sulfuric acid aqueous solution (100ml). Thereafter, the temperature was lowered to O°C. thereto sodium nitrate (5.5g, 79.902mmol) was added, and the reaction mixture was stirred at same temperature for 30 minutes. Then the reaction mixture was stirred at 50To a -70° C. solution of 3-fluoro-4-methyl anisole (1.62 g; 11.6 mmol) in CHPreparation of 3-fluoro-4-methylphenol: 3-Fluoro-4-methylaniline (5g, 39.95 lmmol) was dissolved in 10percent sulfuric acid aqueous solution (100ml). Thereafter, the temperature was lowered to O°C. thereto sodium nitrate (5.5g, 79.902mmol) was added, and the reaction mixture was stirred at same temperature for 30 minutes. Then the reaction mixture was stirred at 50To a -70° C. solution of 3-fluoro-4-methyl anisole (1.62 g; 11.6 mmol) in CHA Grignard reagent prepared from 4-boromo-2-fluorotoluene (25 g, 130 mmol) and magnesium (3.5 g, 140 mmol) by a conventional method was added to a THF solution (200 ml) of trimethyl borate (30 ml, 260 mmol) at a room temperature. After further stirring a night at a room temperature, a 3M hydrochloric acid aqueous solution (100 ml) was added thereto at -20 C. or lower, and the solution was stirred at a room temperature for 2 hours. Brine (150 ml) was added to this reaction mixture, and the solution was extracted with ether (150 ml*2). The solution was dried on anhydrous magnesium sulfate and then filtered, and the solvent was distilled off under reduced pressure, followed by adding heptane (100 ml) to filter non-dissolved crystal off. A 31% hydrogen peroxide aqueous solution (31 ml) was added to a THF solution (300 ml) of the unrefined boric acid derivative (24 g, 160 mmol) obtained above at 0 C., and the solution was stirred a day at a room temperature. A 5% sodium thiosulfate aqueous solution (50 ml) was carefully added to this reaction mixture. 3N hydrochloric acid (100 ml) was further added to the reaction solution, and then the organic layer was separated. The aqueous layer was further extracted with toluene (200 ml), and the organic layers were put together and washed with water (200 ml), followed by drying on anhydrous magnesium sulfate. After filtering, the solvent was distilled off under reduced pressure, and the residue was refined by distillation under reduced pressure (60 C./4.0 mm Hg) to obtain 3-fluoro-4-methylphenol 10 g (60%).To a mixture of To a solution of A mixture of (S)-isopropyl 2-(5-(2-bromoethoxy)-4'-(4, 4-dimethylpiperidin-l- yl)-6'-methyl-[2, 3'-bipyridin]-5'-yl)-2-(tert-butoxy)acetate (35 mg, 0.061 mmol), 3-fluoro-4- methylphenol (11.48 mg, 0.091 mmol) and CS2CO3 (39.6 mg) in DMF (3 mL) was heated at 80 C overnight. Then, the reaction mixture was diluted with 30 mL of EtOAc and washed with water (20 mL x 2). The organic layer was concentrated and the residue was purified by Prep-TLC (pet. ether:EtOAc/l : 1) to give (S)-isopropyl 2-(tert-butoxy)-2-(4'-(4, 4- dimethylpiperidin-l-yl)-5-(2-(3-fluoro-4-methylphenoxy)ethoxy)-6'-methyl-[2, 3'-bipyridin]- 5'-yl)acetate (50 mg, 0.062 mmol, 102 % yield). LCMS (M + H) = 622.Cesium carbonate (1.17 g, 3.59 mmol) was added dropwise to a stirred solution of 3- fluoro-4-methylphenol (250 mg, 1.97 mmol) in DMF (10 mL) at 0C under nitrogen. The resulting solution was stirred 0C for 30 min before 2-fluoro-4-iodopyridine (400 mg, 1.80 mmol) was added. The ice bath was removed, and the mixture was left to stir at room temperature for 18 h. The mixture was hydrolyzed with water, extracted with Et20, the organics were washed with brine, dried over MgSCU and concentrated in vacuo to afford, after purification by silica gel flash chromatography eluting with a gradient of cyclohexane:ethyl acetate - 100:0 to 70:30 the title compound as a white foam (420 mg, 72% yield). ESIMS m/z [M+H]+ 330.18.A solution of A solution of

Molecular Weight:126.13
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:126.048093005
Monoisotopic Mass:126.048093005
Topological Polar Surface Area:20.2
Heavy Atom Count:9
Complexity:94.9
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes