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With thionyl chloride; In methanol; for 2.0h;Reflux;
Example 12 N-(2-cvano- 1 -(5-fluoro- 1 -hydroxy- 1.3 -dihydrobenzo c] [ 1.2"|oxaborol-6-yloxy)propan-2-v l)-4-(trifluoromethoxy)benzamide The solution of 2-bromo-4,5-difluorobenzoic acid (1.00 g, 4.24 mmol) and SOCl2 (2 mL) in MeOH (12 mL) is refluxed for 2 h and cooled to rt. The reaction mixture is evaporated and the residue is purified by column chromatography on silica gel to give the desired product. (0.97 g, 92 % yield).
80.3%
With sulfuric acid; for 4.0h;Reflux;
General procedure: To a solution of 2-bromo-4-fluorobenzoic acid (2.17 g, 10.00 mmol) in methanol (10 mL) was added sulfuric acid (1.63 mL, 30 mmol) , the reaction mixture was refluxed for 4 h.The solvent was removed in vacuo.The mixture was diluted with diethyl ether, and washed water (50 mL * 3) and brine (50 mL * 3), dried over MgSO4. The solvent was removed under reduced pressure.The residue was purified by flash column chromatography with petroleum ether-ethyl acetate (80/1) as eluant to afford colorless liquid. Yield: 88.3%.This compound was prepared according to the general procedure reported by Baker.13 The spectral data were consistent with that reported in the literature.Yield: 80.3%. ESI-MS (m/z): 252.0 [M+1]+.
With hydrogenchloride; In water; for 72.0h;Reflux;
A solution of 2-bromo-4,5-difluorobenzoic acid (5g, 21.10mmol) in methanol was treated with 1 mL of 10M hydrochloric acid and heated to reflux for 72 hours. The reaction mixture was evaporated under vacuum, dissolved in ether and washed with <n="73"/>water before drying (magnesium sulfate) and evaporation to a give the intermediate methyl 2-bromo-4,5-difluorobenzoate (5g) as a colourless oil.
With sulfuric acid; at 0 - 80℃;
To a solution of 2-bromo-4,5-difluoro-benzoic acid (5 g, 21.10 mmol) in methanol (100 ml_) was added concentrated sulfuric acid (0.21 ml_, 2.11 mmol) at 0 C. The reaction mixture was then heated at 80 C for 4 hours. After cooling to room temperature, the mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate, then brine, dried over sodium sulfate, filtered, and concentrated to afford the crude product 2-bromo- 4,5-difluoro-benzoic acid methyl ester (1.48 g, 28%) as a clear oil, which was used in the next step without further purification.
To a solution of R-13 (500 mg, 2.11 mmol) in CH2CI2 (10 mL) is added oxalyl chloride (0.54 mL, 6.33 mmol) dropwise followed by DMF (0.1 mL). The reaction mixture is stirred at room temperature for 0.5 hour and then cooled to 0 C and methanol (1.7 mL, 42.2 mmol) is added. The reaction is warmed to room temperature and stirred for 22 hours and concentrated in vacuo. The residue is dissolved in CH2CI2 and washed with water and brine. The organics are dried with a hydrophobic frit and concentrated in vacuo. The residue is purified by flash chromatography (SiC>2, 50% CH2CI2 in cyclohexane) to give R-14 (501.9 mg).
With caesium carbonate; In acetone; for 1.0h;Reflux;
J15. 6-(5-(benzyloxy)-1H-indol-1-yl)-5-fluorobenzo[c][1,2]oxaborol-1(3H)-ol Methyl 2-bromo-4,5-difluorobenzoate [0219] To a solution of 2-bromo-4,5-diflurorobenzoic acid (23.7g, 10mmol) in acetone (150 mL) were added Cs2C03 (48.8g, 15mmol) and CH3I (lOmL, 15mmol). The mixture was stirred and refluxed for 1 hour then cooled to room temperature. The suspension was diluted with 300 mL petroleum ether. The solid was removed by filtration and washed with petroleum ether. The filtrate was concentrated to give clear oil product. (Yield: 25g, 99.6%). 1HNMR (500 MHz, DMSO-d6) delta 8.00 (t, 1H), 7.92 (t, 1H) and 3.88 (s, 3H) ppm.
To a mixture of 2-bromo-4,5-difluorobenzoic acid (1 g, 4.22 mmol) in dichloromethane (10 mL) and MeOH (1 mL) was added trimethylsilyl)diazomethane (2.110 mL, 4.22 mmol) and the reaction was stirred at rt for 1 h. It was then concentrated to obtain methyl 2-bromo-4,5-difluorobenzoate (1 g, 3.98 mmol, 94% yield) as an oil. 1H NMR (400 MHz, CDCl3) delta 7.76 (dd, J=10.5, 8.3 Hz, 1H), 7.57-7.49 (m, 1H), 3.96 (s, 3H).
2-(ethylsulfonamido)-4,5-difluorobenzoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Step 1: Preparation of 2-(ethylsulfonamido)-4,5-difluorobenzoic acid The titled intermediate was prepared from <strong>[1520-70-3]ethanesulfonamide</strong> (0.78 g, 7.1 mmol) and 2-bromo-4,5-difluorobenzoic acid (1.1 g, 4.8 mmol) according to the conditions of Step 1 of General Synthesis 9. LCMS-ESI- (m/z): [M-H]- calcd 264.02; found 263.96.
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