METHYL5-FLUORO-2-HYDROXYBENZOATE

Pale yellow low melting solid

Preparation of methyl 5-fluorosalicylate (compound 2a):10 g (0.064 mol) of 5-fluorosalicylic acid was dissolved into 60 mL methanol in a 250 mL round-bottom flask with a magnetic stirrer. 5 mL of concentrated sulfuric acid was added dropwise under the ice bath. Upon addition, the mixture was heated under reflux condensation overnight in an oil bath at 80°C. On the next day the reaction mixture was cooled to room temperature and methanol was removed under reduced pressure by rotary evaporator. 60 mL of ethyl acetate was added to the residue and the organic layer was washed with 50 mL of saturated sodium bicarbonate solution and 50 mL of saturated sodium chloride solution in turn. Then the organic layer was dried on anhydrous sodium sulfate and evaporated to dryness. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 150:1) to afford 10.0 g product as a light color oil in 92percent yield. Then the oil solidified to be strip crystal when pumping to dryness by oil pump. Preparation of methyl 5-fluorosalicylate (compound 2a)10 g (0.064 mol) of 5-fluorosalicylic acid was dissolved into 60 mL methanol in a 250 mL round-bottom flask with a magnetic stirrer. 5 mL of concentrated sulfuric acid was added dropwise under the ice bath. Upon addition, the mixture was heated under reflux condensation overnight in an oil bath at 80□.On the next day the reaction mixture was cooled to room temperature and methanol was removed under reduced pressure by rotary evaporator. 60 mL of ethyl acetate was added to the residue and the organic layer was washed with 50 mL of saturated sodium bicarbonate solution and 50 mL of saturated sodium chloride solution in turn. Then the organic layer was dried on anhydrous sodium sulfate and evaporated to dryness. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=150:1) to afford 10.0 g product as a light color oil in 92percent yield. Then the oil solidified to be strip crystal when pumping to dryness by oil pump. To a stirred solution of 5-fluoro salicylic acid (25 g, 160 mmol) in MeOH (250 mL), cone, sulfuric acid (20 mL) was added slowly at 0°C. The resulting reaction mixture was refluxed for 48 h then was concentrated under reduced pressure and the resulting crude was basified to pH 8.0 with sat. NaHC0To a stirred solution of 5-fluoro salicylic acid (25 g, 160 mmol)inMeOH (250 mL), conc. sulfuric acid (20 mL)was added slowly at 0°C.The resulting reaction mixture was refluxed for 48 h then was concentrated under reduced pressure and the resulting crude was basified to pH 8.0 with sat. NaHCO3. The mixture was neutralized by 1 .5 N HCI solution and extracted with EtOAc. The organic layer wasdried over anhydrous Na2504 and concentrated to afford methyl 5-fluoro-2-hydroxybenzoate as a light brown liquid (22.8 g, 83percent yleld). GC-MS (AcqMethod HP-1MS.M) 170.1 (M). 1H NMR (400 MHz, DMSO-d6) 6 ppm 10.29 (5, 1H), 7.51-7.49 (m, 1H), 7.42-7.41 (m, 1H), 7.03-7.01 (m, 1H), 3.89 (5, 3H).Step 1 : To a solution of compound 114 (2.5 g, 16 mmol) in methanol (32 mL) was added sulfuric acid (2.0 mL, 21 mmol). The solution was heated at reflux overnight, cooled to room temperature and concentrated. The residue was dissolved in EtOAc, washed with saturated NaHC0Example 5

Molecular Weight:170.14
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:170.03792224
Monoisotopic Mass:170.03792224
Topological Polar Surface Area:46.5
Heavy Atom Count:12
Complexity:172
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes