(3-bromo-2,4-dimethylphenyl)methanol

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

実験手順: (3-bromo-2,4-dimethylphenyl)methanol (2.0 g, 9.3 mmol), and thalium (III) trifluoroacetate (7.50 g, 14.0 mmol) were added to a 250 mL flask containing a stir bar. The flask was then placed in a cooling bath at 0° C. To the flask was added TFA (150 mL) slowly. The resulting mixture was then stirred at room temperature overnight. The TFA was removed under reduced pressure at 30° C. and the resulting residue was redissolved in dichloroethane and concentrated twice (2×100 mL). The residue was then pumped under high vacuum for 45 min. To the dried residue was then added palladium dichloride (165 mg, 0.930 mmol), lithium chloride (788 mg, 18.6 mmol), and magnesium chloride (750 mg, 18.6 mmol). The resulting mixture was dissolved in MeOH (160 mL). The mixture was then degassed and purged with CO (3 times). The flask under CO was stirred at room temp for 4 hours; the color of the reaction mixture changed from white to cream then to brownish. The color of the reaction then finally changed from brownish to black up on which time the reaction had gone to completion as evidenced by LC as well as TLC (hexanes/EtOAc=1/0.3) analysis. The reaction mixture was then poured into a 1 L Erlenmeyer flask containing DCM (400 mL) and EtOAc (400 mL). The solution was then passed through a celite plug, and rinsed several times with DCM until all the organic material had passed through. The solution was then concentrated to dryness, re-dissolved in DCM, absorbed into silica gel, and separated over silica column to give 5-bromo-4,6-dimethyl-2-benzofuran-1(3H)-one. LC-MS: M+1=242 containing a stir bar The flask was then placed in a cooling bath at 0° C The TFA was removed under reduced pressure at 30° C. the resulting residue was redissolved in dichloroethane concentrated twice (2×100 mL) The residue was then pumped under high vacuum for 45 min The mixture was then degassed purged with CO (3 times) The flask under CO was stirred at room temp for 4 hours The color of the reaction The reaction mixture was then poured into a 1 L Erlenmeyer flask rinsed several times with DCM until all the organic material The solution was then concentrated to dryness re-dissolved in DCM absorbed into silica gel separated over silica column

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

実験手順: 3-Bromo-2,4-dimethylbenzoic acid (6.50 g, 28.4 mmol), in THF (50 mL) was treated with borane tetrahydrofuran complex (42.6 mL, 42.6 mmol) and stirred for 12 h. Analysis by LC indicated that reaction had gone to completion. The solution was concentrated to dryness, redissolved in DCM, and washed with brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The resulting (3-bromo-2,4-dimethylphenyl)methanol was used for the next step with out further purification. 1H-NMR (CDCl3, 500 MHz), δ 7.227 (d, J=7.5 Hz, 1H), 7.122 (d, J=7.5 Hz, 1H), 4.730 (m, 2H), 2.492 (s, 3H), 2.456 (s, 3H). Analysis by LC indicated that reaction The solution was concentrated to dryness redissolved in DCM washed with brine The organic layer was dried over Na2SO4 filtered concentrated The resulting (3-bromo-2,4-dimethylphenyl)methanol was used for the next step with out further purification

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

実験手順: (3-bromo-2,4-dimethylphenyl)methanol (2.0 g, 9.3 mmol), and thalium(III) trifluoroacetate (7.50 g, 14.0 mmol) were added to a 250 mL flask containing a stir bar. The flask was then placed in a cooling bath at 0° C. To the flask was added TFA (150 mL) slowly. The resulting mixture was then stirred at room temperature overnight. The TFA was removed under reduced pressure at 30° C. and the resulting residue was redissolved in dichloroethane and concentrated twice (2×100 mL). The residue was then pumped under high vacuum for 45 min. To the dried residue was then added palladium dichloride (165 mg, 0.930 mmol), lithium chloride (788 mg, 18.6 mmol), and magnesium chloride (750 mg, 18.6 mmol). The resulting mixture was dissolved in MeOH (160 mL). The mixture was then degassed and purged with CO (3 times). The flask under CO was stirred at room temp for 4 hours; the color of the reaction mixture changed from white to cream then to brownish. The color of the reaction then finally changed from brownish to black up on which time the reaction had gone to completion as evidenced by LC as well as TLC (hexanes/EtOAc=1/0.3) analysis. The reaction mixture was then poured into a 1 L Erlenmeyer flask containing DCM (400 mL) and EtOAc (400 mL). The solution was then passed through a celite plug, and rinsed several times with DCM until all the organic material had passed through. The solution was then concentrated to dryness, re-dissolved in DCM, absorbed into silica gel, and separated over silica column to give 5-bromo-4,6-dimethyl-2-benzofuran-1(3H)-one. LC-MS: M+1=242 containing a stir bar The flask was then placed in a cooling bath at 0° C The TFA was removed under reduced pressure at 30° C. the resulting residue was redissolved in dichloroethane concentrated twice (2×100 mL) The residue was then pumped under high vacuum for 45 min The mixture was then degassed purged with CO (3 times) The flask under CO was stirred at room temp for 4 hours The color of the reaction The reaction mixture was then poured into a 1 L Erlenmeyer flask rinsed several times with DCM until all the organic material The solution was then concentrated to dryness re-dissolved in DCM absorbed into silica gel separated over silica column

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

実験手順: 3-Bromo-2,4-dimethylbenzoic acid (6.50 g, 28.4 mmol), in THF (50 mL) was treated with borane tetrahydrofuran complex (42.6 mL, 42.6 mmol) and stirred for 12 h. Analysis by LC indicated that reaction had gone to completion. The solution was concentrated to dryness, redissolved in DCM, and washed with brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The resulting (3-bromo-2,4-dimethylphenyl)methanol was used for the next step with out further purification. 1H-NMR (CDCl3, 500 MHz), δ 7.227 (d, J=7.5 Hz, 1H), 7.122 (d, J=7.5 Hz, 1H), 4.730 (m, 2H), 2.492 (s, 3H), 2.456 (s, 3H). Analysis by LC indicated that reaction The solution was concentrated to dryness redissolved in DCM washed with brine The organic layer was dried over Na2SO4 filtered concentrated The resulting (3-bromo-2,4-dimethylphenyl)methanol was used for the next step with out further purification