* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With hydrogenchloride; In tetrahydrofuran; hexane; Petroleum ether;
t-Butyllithium (1.7 ml of a 1.8M solution of hexane; 3 equiv.) is added to THF (1 ml) and cooled to -78 C. under argon with stirring, and a solution of <strong>[2844-05-5]2-bromo-6-trifluoromethylphenol</strong> in dry THF (1 ml; 1 mmol) is added dropwise via syringe. The reaction is stirred 30 minutes, and then iodomethane (340 mg; 2.4 equiv.) is added dropwise via syringe at -78 C. under argon, with stirring. The mixture is allowed to warm to 0 C. with stirring over 15 minutes, and stirring is continued for 45 minutes more. The reaction is then quenched with 1N HCl (3 ml) and extracted from 1N HCl (10 ml) with 3*10 ml portions of ether. The combined ether portions are washed with water (3*20 ml portions: pH tests neutral), and the solution is then dried (MgSO4), filtered, and concentrated in vacuo to give crude 2-methyl-6-trifluoromethylphenol, which is chromatographed on silica gel with 5% ether in petroleum ether to give pure product.
With hydrogenchloride; In tetrahydrofuran; hexane; Petroleum ether;
t-Butyllithium (1.7 ml of a 1.8M solution of hexane; 3 equiv.) is added to THF (1 ml) and cooled to -78 C. under argon with stirring, and a solution of <strong>[2844-05-5]2-bromo-6-trifluoromethylphenol</strong> in dry THF (1 ml; 1 mmol) is added dropwise via syringe. The reaction is stirred 30 minutes, and then iodomethane (340 mg; 2.4 equiv.) is added dropwise via syringe at -78 C. under argon, with stirring. The mixture is allowed to warm to 0 C. with stirring over 15 minutes, and stirring is continued for 45 minutes more. The reaction is then quenched with 1N HCl (3 ml) and extracted from 1N HCl (10 ml) with 3*10 ml portions of ether. The combined ether portions are washed with water (3*20 ml portions: pH tests neutral), and the solution is then dried (MgSO4), filtered, and concentrated in vacuo to give crude 2-methyl-6 -trifluoromethylphenol, which is chromatographed on silica gel with 5% ether in petroleum ether to give pure product.
With hydrogenchloride; bromine; In tetrahydrofuran; dichloromethane; water;
EXAMPLE 4 Synthesis of 2-Methyl-4-(5'-hexynoyl)-6-trifluoromethylphenol STR20 To a solution of o-trifluoromethylphenol (3.0 g; 19 mmol) in CH2 Cl2 (20 ml) is added bromine (6.4 g; 39.9 mmol) at 25 C. with stirring, and stirring is continued for 2.5 hours. The reaction is then poured into a separatory funnel with 100 ml of water plus 100 ml ether. The aqueous portion is extracted with 3*100 ml portions of ether. The organic fractions are combined and washed with 1M sodium bicarbonate (300 ml) followed by a water (200 ml) wash. The mixture is then dried (MgSO4), filtered, and concentrated in vacuo to give 5.8 g crude 2,4-dibromo-6-trifluoromethylphenol. To remove contaminating mono-brominated material, the reaction above is repeated on the crude product (6.4 g bromine) to give pure product (5.77 g of 2,4-dibromo-6-trifluoromethylphenol) used in the next step without further purification. A solution of 2,4-dibromo-6-trifluoromethylphenol (5.77 g; 18 mmol) is dissolved in dry THF (45 ml), and s-butyllithium (21 ml of 1.7M solution) is added dropwise with stirring at -78 C. under argon. After stirring at -78 C. for 30 minutes, the mixture is allowed to warm to 0 C. and is stirred 40 minutes more. The reaction is quenched with 1N HCl and extracted from 1N HCl (50 ml) with 3*50 ml portions of ether. The combined ether portions are washed with 1M sodium bicarbonate (100 ml) then dried (MgSO4), filtered and concentrated in vacuo to give 3.84 g crude product. Chromatography on silica gel (95:5 petroleum ether/ether) thus gives 2-bromo-6-trifluoromethylphenol.
With hydrogenchloride; bromine; In tetrahydrofuran; dichloromethane; water;
EXAMPLE 13 2-methyl-4-(5'-hexynoyl)-6-trifluoromethylphenol STR37 To a solution of o-trifluoromethylphenol (3.0 g; 19 mmol) in CH2 Cl2 (20 ml) is added bromine (6.4 g; 39.9 mmol) at 25 C. with stirring, and stirring is continued for 2.5 hours. The reaction is then poured into a separatory funnel with 100 ml of water plus 100 ml ether. The aqueous portion is extracted with 3*100 ml portions of ether. The organic fractions are combined and washed with 1M sodium bicarbonate (300 ml) followed by a water (200 ml) wash. The mixture is then dried (MgSO4), filtered, and concentrated in vacuo to give 5.8 g crude 2,4-dibromo-6-trifluoromethylphenol. To remove contaminating mono-brominated material, the reacting above is repeated on the crude product (6.4 g bromine) to give pure product (5.77 g of 2,4-dibromo-6-trifluoromethylphenol) used in the next step without further purification. A solution of 2,4-dibromo-6-trifluoromethylphenol (5.77; 18 mmol) is dissolved in dry THF (45 ml), and s-butyllithium (21 ml of 1.7M solution) is added dropwise with stirring at -78 C. under argon. After stirring at -78 C. for 30 minutes, the mixture is allowed to warm to 0 C. and is stirred 40 minutes more. The reaction is quenched with 1N HCl and extracted from 1N HCl (50 ml) with 3*50 ml portions of ether. The combined ether portions are washed with 1M sodium bicarbonate (100 ml) then dried (MgSO4), filtered and concentrated in vacuo to give 3.84 g crude product. Chromatography on silica gel (95:5 petroleum ether/ether) thus gives 2-bromo-6-trifluoromethylphenol.
tert-butyl 4-bromo-2-(2-bromo-6-(trifluoromethyl)phenoxy)butanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
21%
With potassium carbonate; In N,N-dimethyl-formamide; at 100.0℃;Inert atmosphere;
A round-bottom flask was charged with <strong>[2844-05-5]2-bromo-6-(trifluoromethyl)phenol</strong> (0.500 g, 2.07 mmol, 1.00 equiv), tert-butyl 2,4-dibromobutanoate (1.25 g, 4.14 mmol, 2.00 equiv), potassium carbonate (0.857 g, 6.21 mmol, 3.00 equiv) and DMF (15 mL) under nitrogen. The reaction mixture was stirred overnight at 100 C. and quenched with water (10 mL). The resulting solution was extracted with EtOAc (3*20 mL), and the organic layers were combined, washed with brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 0.200 g (21% yield) of tert-butyl 4-bromo-2-(2-bromo-6-(trifluoromethyl)phenoxy)butanoate. LCMS (ESI, m/z): 461 [M+H]+.