Methyl 4-bromo-2-fluorobenzoate

off-white powder

4- (8, 8-DIMETHYL-5-P-TOLYL-7, 8-dihydro-2- NAPHTHYLSELANYLETHYNYL)-2-FLUOROBENZOIC acid a. Methyl 4-BROMO-2-FLUOROBENZOATE 5 g (23 mmol) of 4-bromo-2-fluorobenzoic acid are dissolved in methanol with a few drops of sulphuric acid. The reaction medium is refluxed for 20 hours, hydrolysed and extracted with ethyl acetate. A white solid is obtained (5.6 g; yield = 100percent).To a solution of 4 (13.1 g, 60.0 mmol) in methanol (60 mL) was slowly added SOCk (12 mL) at 0 °C. After stirring overnight (ca. 12 h) at ambient temperature, the solvent was removed under reduced pressure, and the reaction mixture was basified with saturated NaHCCte at 0 °C. Ether (200 mL) was added to the crude mixture, which was washed with saturated NaHCCte (100 mL x 2) and brine (50 mL x 2). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The product mixture was purified by flash chromatography to provide the title product 8 as a white solid (13.4 g, 58 mmol, 96percent). NMR (400 MHz, CDCb) δ 7.86 - 7.78 (m, 1H), 7.39 - 7.30 (m, 2H), 3.92 (s, 2H). Step 1 : To a stirred solution of 4-bromo-2-fluorobenzoic acid (15.0 g, 68.49 mmol, 1 eq) in MeOH (150 mL), SOCIStep 1 (0320) To a solution of compound 3a (50 g, 210 mmol) in DCM (300 mL) was added oxalyl dichloride (40.38 g, 300 mmol) dropwise at room temperature. The reaction mixture was stirred at room temperature for lh. Then MeOH (50 ml) was added dropwise, the solution was stirred at room temperature for another lh. The solvent was removed to afford compound 3b (48 g, 93percent).Example 109AMethyl 4-bromo-2-fluorobenzoic acid; 4-bromo-2-fluorobenzoic acid (30 g, 0.14 mol) was dissolved in methanol with a few drops of sulfuric acid. The reaction medium was refluxed for 20 hours. The cooled reaction mixture was evaporated and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic layer was separated and washed with brine, dried over sodium sulfate, filtered and evaporated to give methyl 4-bromo-2-fluorobenzoate (20.7 g, yield 64percent) as a white solid. 4-Bromo-2]DIFFDT_1[-FF]IDDT_21[uorobenzonic acid (2a) (5.0 kg, 22.9 mol) was charged to a 50-L round-bottom glass reaction vessel holding methanol (20.0 L). Concentrated sulfuric acid (500 mL) was added dropwise over 40 min. The reaction mixture was heated under reux for 12 h, poured into ice water (30 L) and the white solid precipitateDDIF]F_T51[ was ltered. The product was dried by heating (less than 50 °C) in an oven overnight to afford 2b as white crystals (4851.1 g, 91.2percent yield). Mp 60.0–61.0 °C; 1IFF]DDT_8[H NMR (400 Hz, DMSO-dMethyl iodide (1.49 mL, 24 mmol) was added to asuspension of 4-bromo-2-fluorobenzoic acid (4.38 g, 20 mmol) and sodium carbonate (6.36 g, 60 mmol) in dimethylformamide (50 mL), and the mixture was stirred overnight at room temperature. After completion of the reaction, ethyl acetate was added, and the mixture was washed with water and a saturated ammonium chloride aqueous solution. After drying over magnesium sulfate, concentration was carried out to obtain 4.50 g of the desired product as a colorless solid (yield 97percent). ^oH-NMR (ppm in CDC13) d 3.93 (s, 3H), 7.33-7.38 (m, 2H), 7.80-7.85 (m, 1H).STEP 1 : To a solution of 4-bromo-2-fluorobenzoic acid (2.0 g, 9.1 mmol) in THF (24 mL) and methanol (6 mL) at 0 °C was added a solution of (trimethylsilyl)diazomethane in hexanes (2.0 M, 5.46 mL, 10.9 mmol). The yellow solution was allowed to gradually warm to room temperature over 1 h. The volatile materials were removed and the residue was treated with aqueous hydrochloric acid (1 M). The aqueous mixture was extracted with ethyl acetate. The organic extract was dried over magnesium sulfate, filtered, and concentrated to provide crude methyl 4- bromo-2-fluorobenzoate (2.7 g, quantitative yield). This material was used in the subsequent step without further purification. Example 35A To a suspension of compound 5-10 (12 g, 54.79 mmol) in DCM (120 mL) was added oxalyl chloride (COCl) (10.43 g, 82.19 mmol) and two drops of DMF in a catalytic quantity at 0° C. under nitrogen atmosphere, and then the reaction solution was reacted under nitrogen atmosphere at r.t. for 3 h. Then the solvent was removed, MeOH (100 mL) was added, and the resulting reaction solution was reacted at r.t. for 18 h. After TLC indicated the reaction was complete, the reaction solution was concentrated, and the residue was dissolved in EtOAc (100 mL) and washed with saturated Na

Molecular Weight:233.03
XLogP3:2.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:231.95352
Monoisotopic Mass:231.95352
Topological Polar Surface Area:26.3
Heavy Atom Count:12
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes