ethyl 2-(2,6-dimethylphenyl)acetate

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A dry Schlenk vessel was initially charged with 185 mg [1 mmol] of 2,6-dimethylbromobenzene, 1056 mg [6.6 mmol] of diethyl malonate, 2.88 mg [0.005 mmol] of Pd(dba)2, 3.19 mg [0.011 mmol] of P(tert-Bu)3×HBF4, 207 mg [1.5 mmol] of dried K2CO3 and 150 mg [1.5 mmol] of KHCO3. The reaction vessel was three times evacuated and filled with nitrogen. This was followed by stirring at 160° C. until completion of conversion (8 hours). After cooling to room temperature, the reaction mixture was diluted with ethyl acetate. The resulting solution was washed successively with 20 ml each of water, saturated aq. NaHCO3 solution and saturated aqueous NaCl solution, dried over MgSO4, filtered and concentrated under reduced pressure. Chromatographic purification using silica gel (hexane/ethyl acetate) gave ethyl 2,6-dimethylphenylacetate in a yield of 81% of theory. evacuated filled with nitrogen After cooling to room temperature the reaction mixture was diluted with ethyl acetate The resulting solution was washed successively with 20 ml each of water, saturated aq. NaHCO3 solution and saturated aqueous NaCl solution dried over MgSO4 filtered concentrated under reduced pressure Chromatographic purification

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

実験手順: To a mixture of (2,6-dimethyl-phenyl)-acetic acid ethyl ester (13.3 g, 69.2 mmol) in THF (550 mL) and water (224 mL) was added lithium hydroxide monohydrate (23.2 g, 553 mmol). The resulting mixture was stirred vigorously at rt. After 72 h, the mixture was heated to 50° C. for an additional 24 h. The mixture was cooled to rt and concentrated. To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate. The precipitate was collected by vacuum filtration and further purified by FCC to provide a colorless solid (8.9 g, 78%). MS (ESI): mass calcd. for C10H12O2, 164.1; m/z found, 163.1 [M−H]+. 1H NMR (CDCl3): 7.17-6.90 (m, 3H), 3.72 (s, 2H), 2.33 (s, 6H). the mixture was heated to 50° C. for an additional 24 h The mixture was cooled to rt concentrated To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate The precipitate was collected by vacuum filtration further purified by FCC

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

実験手順: To a mixture of (2,6-dimethyl-phenyl)-acetic acid ethyl ester (13.3 g, 69.2 mmol) in THF (550 mL) and water (224 mL) was added lithium hydroxide monohydrate (23.2 g, 553 mmol). The resulting mixture was stirred vigorously at rt. After 72 h, the mixture was heated to 50° C. for an additional 24 h. The mixture was cooled to rt and concentrated. To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate. The precipitate was collected by vacuum filtration and further purified by FCC to provide a colorless solid (8.9 g, 78%). MS (ESI): mass calcd. for C10H12O2, 164.1; m/z found, 163.1 [M−H]+. 1H NMR (CDCl3): 7.17-6.90 (m, 3H), 3.72 (s, 2H), 2.33 (s, 6H). the mixture was heated to 50° C. for an additional 24 h The mixture was cooled to rt concentrated To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate The precipitate was collected by vacuum filtration further purified by FCC

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

実験手順: To a mixture of (2,6-dimethyl-phenyl)-acetic acid ethyl ester (13.3 g, 69.2 mmol) in THF (550 mL) and water (224 mL) was added lithium hydroxide monohydrate (23.2 g, 553 mmol). The resulting mixture was stirred vigorously at rt. After 72 h, the mixture was heated to 50° C. for an additional 24 h. The mixture was cooled to rt and concentrated. To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate. The precipitate was collected by vacuum filtration and further purified by FCC to provide a colorless solid (8.9 g, 78%). MS (ESI): mass calcd. for C10H12O2, 164.1; m/z found, 163.1 [M−H]+. 1H NMR (CDCl3): 7.17-6.90 (m, 3H), 3.72 (s, 2H), 2.33 (s, 6H). the mixture was heated to 50° C. for an additional 24 h The mixture was cooled to rt concentrated To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate The precipitate was collected by vacuum filtration further purified by FCC

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

実験手順: To a mixture of (2,6-dimethyl-phenyl)-acetic acid ethyl ester (13.3 g, 69.2 mmol) in THF (550 mL) and water (224 mL) was added lithium hydroxide monohydrate (23.2 g, 553 mmol). The resulting mixture was stirred vigorously at rt. After 72 h, the mixture was heated to 50° C. for an additional 24 h. The mixture was cooled to rt and concentrated. To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate. The precipitate was collected by vacuum filtration and further purified by FCC to provide a colorless solid (8.9 g, 78%). MS (ESI): mass calcd. for C10H12O2, 164.1; m/z found, 163.1 [M−H]+. 1H NMR (CDCl3): 7.17-6.90 (m, 3H), 3.72 (s, 2H), 2.33 (s, 6H). the mixture was heated to 50° C. for an additional 24 h The mixture was cooled to rt concentrated To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate The precipitate was collected by vacuum filtration further purified by FCC

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A dry Schlenk vessel was initially charged with 185 mg [1 mmol] of 2,6-dimethylbromobenzene, 1056 mg [6.6 mmol] of diethyl malonate, 2.88 mg [0.005 mmol] of Pd(dba)2, 3.19 mg [0.011 mmol] of P(tert-Bu)3×HBF4, 207 mg [1.5 mmol] of dried K2CO3 and 150 mg [1.5 mmol] of KHCO3. The reaction vessel was three times evacuated and filled with nitrogen. This was followed by stirring at 160° C. until completion of conversion (8 hours). After cooling to room temperature, the reaction mixture was diluted with ethyl acetate. The resulting solution was washed successively with 20 ml each of water, saturated aq. NaHCO3 solution and saturated aqueous NaCl solution, dried over MgSO4, filtered and concentrated under reduced pressure. Chromatographic purification using silica gel (hexane/ethyl acetate) gave ethyl 2,6-dimethylphenylacetate in a yield of 81% of theory. evacuated filled with nitrogen After cooling to room temperature the reaction mixture was diluted with ethyl acetate The resulting solution was washed successively with 20 ml each of water, saturated aq. NaHCO3 solution and saturated aqueous NaCl solution dried over MgSO4 filtered concentrated under reduced pressure Chromatographic purification

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

実験手順: To a mixture of (2,6-dimethyl-phenyl)-acetic acid ethyl ester (13.3 g, 69.2 mmol) in THF (550 mL) and water (224 mL) was added lithium hydroxide monohydrate (23.2 g, 553 mmol). The resulting mixture was stirred vigorously at rt. After 72 h, the mixture was heated to 50° C. for an additional 24 h. The mixture was cooled to rt and concentrated. To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate. The precipitate was collected by vacuum filtration and further purified by FCC to provide a colorless solid (8.9 g, 78%). MS (ESI): mass calcd. for C10H12O2, 164.1; m/z found, 163.1 [M−H]+. 1H NMR (CDCl3): 7.17-6.90 (m, 3H), 3.72 (s, 2H), 2.33 (s, 6H). the mixture was heated to 50° C. for an additional 24 h The mixture was cooled to rt concentrated To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate The precipitate was collected by vacuum filtration further purified by FCC

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 25 ml three-neck flask with magnetic stirrer, reflux condenser and dropping funnel is initially charged with 20 ml of tetrahydrofuran (THF) which has been dried over molecular sieve, and 0.36 ml of water. The mixture is heated to 50° C. while passing argon through for a few minutes, and then cooled again to room temperature. Still under argon, the following are now added: 17.2 mg [0.03 mmol=0.3 mol %] of bis(dibenzylideneacetone)palladium, 27.4 mg of P(o-tolyl)3 [0.09 mmol], 2.91 g of potassium fluoride (dried over P2O5 at 140° C.), 1.5 g [10 mmol] of 2,6-dimethylphenylboronic acid and 2.56 g [15 mmol] of ethyl bromoacetate. This mixture is stirred under reflux in a gentle argon stream for 24 hours. Then it is filtered through a little Celite, and the filtercake is washed three times with 20 ml each time of ethyl acetate. The combined filtrates are extracted by shaking with 20 ml of 1 N hydrochloric acid. The aqueous phase is re-extracted twice with 20 ml of ethyl acetate each time. The combined organic phases are then washed with 20 ml of saturated aqueous NaCl solution, dried and concentrated. This gives 1.59 g of an oil which, according to GC-MS, as well as 10.7 area % of m-xylene, contains 56.6 area % of ethyl 2,6-dimethylphenylacetate. This corresponds to a yield of 46.8% of theory. A 25 ml three-neck flask with magnetic stirrer, reflux condenser has been dried over molecular sieve, and 0.36 ml of water through for a few minutes cooled again to room temperature Still under argon, the following are now added under reflux in a gentle argon Then it is filtered through a little Celite the filtercake is washed three times with 20 ml each time of ethyl acetate The combined filtrates are extracted by shaking with 20 ml of 1 N hydrochloric acid The aqueous phase is re-extracted twice with 20 ml of ethyl acetate each time The combined organic phases are then washed with 20 ml of saturated aqueous NaCl solution dried concentrated

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 25 ml three-neck flask with magnetic stirrer, reflux condenser and dropping funnel is initially charged with 20 ml of tetrahydrofuran (THF) which has been dried over molecular sieve. The THF is heated to 50° C. while passing argon through for a few minutes, and then cooled again to room temperature. Still under argon, the following are now added: 17.2 mg [0.03 mmol=0.3 mol %] of bis(dibenzylideneacetone)palladium, 27.4 mg of P(o-tolyl)3 (tri-o-tolylphosphine) [0.09 mmol], 2.91 g of potassium fluoride (dried over P2O5 at 140° C.), 272 mg [1 mmol=10 mol %] of benzyltriethylammonium bromide, 1.5 g [10 mmol] of 2,6-dimethylphenylboronic acid and 2.56 g [15 mmol] of ethyl bromoacetate. This mixture is stirred under reflux in a gentle argon stream for 24 hours. Then it is filtered through a little Celite, and the filtercake is washed three times with 20 ml each time of ethyl acetate. The combined filtrates are extracted by shaking with 20 ml of 1 N hydrochloric acid. The aqueous phase is re-extracted twice with 20 ml of ethyl acetate each time. The combined organic phases are then washed with 20 ml of saturated aqueous NaCl solution, dried and concentrated. This gives 2.16 g of an oil which, according to GC-MS, as well as 8.9 area % of m-xylene, contains 72.9 area % of ethyl 2,6-dimethylphenylacetate. This corresponds to a yield of 81.9% of theory. A 25 ml three-neck flask with magnetic stirrer, reflux condenser has been dried over molecular sieve through for a few minutes cooled again to room temperature Still under argon, the following are now added under reflux in a gentle argon Then it is filtered through a little Celite the filtercake is washed three times with 20 ml each time of ethyl acetate The combined filtrates are extracted by shaking with 20 ml of 1 N hydrochloric acid The aqueous phase is re-extracted twice with 20 ml of ethyl acetate each time The combined organic phases are then washed with 20 ml of saturated aqueous NaCl solution dried concentrated

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A dry Schlenk vessel was initially charged with 185 mg [1 mmol] of 2,6-dimethylbromobenzene, 1056 mg [6.6 mmol] of diethyl malonate, 2.88 mg [0.005 mmol] of Pd(dba)2, 3.19 mg [0.011 mmol] of P(tert-Bu)3×HBF4, 207 mg [1.5 mmol] of dried K2CO3 and 150 mg [1.5 mmol] of KHCO3. The reaction vessel was three times evacuated and filled with nitrogen. This was followed by stirring at 160° C. until completion of conversion (8 hours). After cooling to room temperature, the reaction mixture was diluted with ethyl acetate. The resulting solution was washed successively with 20 ml each of water, saturated aq. NaHCO3 solution and saturated aqueous NaCl solution, dried over MgSO4, filtered and concentrated under reduced pressure. Chromatographic purification using silica gel (hexane/ethyl acetate) gave ethyl 2,6-dimethylphenylacetate in a yield of 81% of theory. evacuated filled with nitrogen After cooling to room temperature the reaction mixture was diluted with ethyl acetate The resulting solution was washed successively with 20 ml each of water, saturated aq. NaHCO3 solution and saturated aqueous NaCl solution dried over MgSO4 filtered concentrated under reduced pressure Chromatographic purification

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

実験手順: To a mixture of (2,6-dimethyl-phenyl)-acetic acid ethyl ester (13.3 g, 69.2 mmol) in THF (550 mL) and water (224 mL) was added lithium hydroxide monohydrate (23.2 g, 553 mmol). The resulting mixture was stirred vigorously at rt. After 72 h, the mixture was heated to 50° C. for an additional 24 h. The mixture was cooled to rt and concentrated. To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate. The precipitate was collected by vacuum filtration and further purified by FCC to provide a colorless solid (8.9 g, 78%). MS (ESI): mass calcd. for C10H12O2, 164.1; m/z found, 163.1 [M−H]+. 1H NMR (CDCl3): 7.17-6.90 (m, 3H), 3.72 (s, 2H), 2.33 (s, 6H). the mixture was heated to 50° C. for an additional 24 h The mixture was cooled to rt concentrated To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate The precipitate was collected by vacuum filtration further purified by FCC

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

実験手順: To a mixture of (2,6-dimethyl-phenyl)-acetic acid ethyl ester (13.3 g, 69.2 mmol) in THF (550 mL) and water (224 mL) was added lithium hydroxide monohydrate (23.2 g, 553 mmol). The resulting mixture was stirred vigorously at rt. After 72 h, the mixture was heated to 50° C. for an additional 24 h. The mixture was cooled to rt and concentrated. To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate. The precipitate was collected by vacuum filtration and further purified by FCC to provide a colorless solid (8.9 g, 78%). MS (ESI): mass calcd. for C10H12O2, 164.1; m/z found, 163.1 [M−H]+. 1H NMR (CDCl3): 7.17-6.90 (m, 3H), 3.72 (s, 2H), 2.33 (s, 6H). the mixture was heated to 50° C. for an additional 24 h The mixture was cooled to rt concentrated To the resulting residue was added aqueous 2 N HCl (300 mL) to afford a colorless precipitate The precipitate was collected by vacuum filtration further purified by FCC