methyl 4-hydroxy-2-(trifluoromethyl)benzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 4-hydroxy-2-(trifluoromethyl)benzoate (32.0 g) was dissolved in acetic acid (180 ml), and thereto was added conc. sulfuric acid (0.45 ml), and the mixture was heated to 65° C. Then, thereto was slowly added a 70% solution of conc. nitric acid (12.4 g) in acetic acid (60 ml) dropwise, and the mixture was stirred at 65° C. for one hour. The reaction mixture was cooled to room temperature, and poured into ice-water (500 ml), and the mixture was extracted twice with toluene (800 ml). The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (15.0 g). The reaction mixture was cooled to room temperature the mixture was extracted twice with toluene (800 ml) The organic layer was washed with water a saturated aqueous sodium chloride solution, dried over sodium sulfate filtered concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Hydroxy-2-(trifluoromethyl)benzoic acid (30.0 g) was dissolved in methanol (600 ml), thereto was added dropwise conc. sulfuric acid (10 ml). Then, the mixture was refluxed with stirring for 20 hours. The mixture was cooled to room temperature, and to the reaction mixture was added water (200 ml), and methanol was removed by evaporation, and the resultant was extracted twice with ethyl acetate (300 ml). The organic layer was washed with water, a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (32.0 g). Then, the mixture was refluxed was removed by evaporation the resultant was extracted twice with ethyl acetate (300 ml) The organic layer was washed with water a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, dried over sodium sulfate filtered concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-hydroxy-2-trifluoromethyl-benzoic acid methyl ester (1.1 g, 4.8 mmol, 1.0 eq) was dissolved in acetone (14 mL), NaI (0.5 eq) and K2CO3 (1.04 g, 2.0 eq) were added and the mixture was stirred at room temperature for 30 min. (Bromomethyl)cyclopropane (0.42 mL, 4.3 mmol, 0.9 eq) was added, and the mixture was refluxed for 2 days. The solvent was concentrated under reduced pressure, NaOH 10% was added, and it was extracted with DCM and dried. The title product (1.21 g, yield 92%) was recovered and used without further purification. was added the mixture was refluxed for 2 days The solvent was concentrated under reduced pressure, NaOH 10% was added it was extracted with DCM dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-hydroxy-2-trifluoromethyl-benzoic acid (5.0 g, 24.0 mmol) was dissolved in MeOH (50 mL) and a catalytic quantity of sulfuric acid was added. The mixture was refluxed overnight, after which the solvent was evaporated under reduced pressure; the crude was dissolved in DCM and washed with saturated NaHCO3. The organic phase was dried and evaporated under reduced pressure, and the product was used without further purification. The mixture was refluxed overnight after which the solvent was evaporated under reduced pressure the crude was dissolved in DCM washed with saturated NaHCO3 The organic phase was dried evaporated under reduced pressure the product was used without further purification