4-bromo-2-methoxy-1-propan-2-yloxybenzene

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under an atmosphere of nitrogen, tert-butyllithium (2.14 mL of 1.6 M in toluene, 3.42 mmol) was added dropwise to a solution of 4-bromo-1-isopropoxy-2-methoxy-benzene (400 mg, 1.63 mmol) in THF (6 mL) at −78° C. The reaction mixture was allowed to stir for 1 hour at −78° C., then added dropwise to a flask containing CO2 (1.8 g, 40.8 mmol) (solid, dry ice) in THF (2 mL). The reaction mixture was allowed to stir for 30 minutes warming to room temperature. Water (20 mL) was added to the reaction mixture and the volatiles were removed in vacuo. The resultant aqueous layer was acidified with 1N HCl solution to pH 1 and was extracted with ethyl acetate (3×15 mL). The organics were separated and the combined organics were washed with brine solution, dried over sodium sulfate, filtered and concentrated in vacuo to give 4-isopropoxy-3-methoxy-benzoic acid (310 mg, 85%) as a white solid. ESI-MS m/z calc. 210.1. found 211.1 (M+1)+; Retention time: 1.23 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 12.63 (s, 1H), 7.53 (dd, J=8.4, 2.0 Hz, 1H), 7.44 (d, J=2.0 Hz, 1H), 7.04 (d, J=8.7 Hz, 1H), 4.67 (dt, J=12.1, 6.0 Hz, 1H), 3.78 (s, 3H), 1.28 (d, J=6.0 Hz, 6H). added dropwise to a flask to stir for 30 minutes warming to room temperature the volatiles were removed in vacuo was extracted with ethyl acetate (3×15 mL) The organics were separated the combined organics were washed with brine solution dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromopropane (3.39 mL, 36.2 mmol) was added to a suspension of 4-bromo-2-methoxy-phenol (5 g, 24.1 mmol), K2CO3 (6.67 g, 48.3 mmol) and DMSO (71 mL) at room temperature. The heterogeneous mixture was stirred at 55° C. for 2 hours, then cooled to room temperature and diluted with water. The reaction mixture was extracted with Et2O and the extract was washed successively with 10% aq. NaOH solution, water, then brine solution. The organics were separated and dried over sodium sulfate, filtered and concentrated in vacuo to give 4-bromo-1-isopropoxy-2-methoxy-benzene (5.83 g, 94%) as a pale yellow oil. ESI-MS m/z calc. 244.0. found 245.0 (M+1)+; Retention time: 1.93 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.03-6.95 (m, 2H), 6.76 (dd, J=7.7, 1.1 Hz, 1H), 4.47 (dt, J=12.2, 6.1 Hz, 1H), 3.84 (s, 3H), 1.35 (d, J=6.1 Hz, 6H). cooled to room temperature The reaction mixture was extracted with Et2O the extract was washed successively with 10% aq. NaOH solution, water The organics were separated dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromopropane (3.39 mL, 36.2 mmol) was added to a suspension of 4-bromo-2-methoxy-phenol (5 g, 24.1 mmol), K2CO3 (6.67 g, 48.3 mmol) and DMSO (71 mL) at room temperature. The heterogeneous mixture was stirred at 55° C. for 2 hours, then cooled to room temperature and diluted with water. The reaction mixture was extracted with Et2O and the extract was washed successively with 10% aq. NaOH solution, water, then brine solution. The organics were separated and dried over sodium sulfate, filtered and concentrated in vacuo to give 4-bromo-1-isopropoxy-2-methoxy-benzene (5.83 g, 94%) as a pale yellow oil. ESI-MS m/z calc. 244.0. found 245.0 (M+1)+; Retention time: 1.93 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.03-6.95 (m, 2H), 6.76 (dd, J=7.7, 1.1 Hz, 1H), 4.47 (dt, J=12.2, 6.1 Hz, 1H), 3.84 (s, 3H), 1.35 (d, J=6.1 Hz, 6H). cooled to room temperature The reaction mixture was extracted with Et2O the extract was washed successively with 10% aq. NaOH solution, water The organics were separated dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under an atmosphere of nitrogen, tert-butyllithium (2.14 mL of 1.6 M in toluene, 3.42 mmol) was added dropwise to a solution of 4-bromo-1-isopropoxy-2-methoxy-benzene (400 mg, 1.63 mmol) in THF (6 mL) at −78° C. The reaction mixture was allowed to stir for 1 hour at −78° C., then added dropwise to a flask containing CO2 (1.8 g, 40.8 mmol) (solid, dry ice) in THF (2 mL). The reaction mixture was allowed to stir for 30 minutes warming to room temperature. Water (20 mL) was added to the reaction mixture and the volatiles were removed in vacuo. The resultant aqueous layer was acidified with 1N HCl solution to pH 1 and was extracted with ethyl acetate (3×15 mL). The organics were separated and the combined organics were washed with brine solution, dried over sodium sulfate, filtered and concentrated in vacuo to give 4-isopropoxy-3-methoxy-benzoic acid (310 mg, 85%) as a white solid. ESI-MS m/z calc. 210.1. Found 211.1 (M+1)+; Retention time: 1.23 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 12.63 (s, 1H), 7.53 (dd, J=8.4, 2.0 Hz, 1H), 7.44 (d, J=2.0 Hz, 1H), 7.04 (d, J=8.7 Hz, 1H), 4.67 (dt, J=12.1, 6.0 Hz, 1H), 3.78 (s, 3H), 1.28 (d, J=6.0 Hz, 6H). added dropwise to a flask to stir for 30 minutes warming to room temperature the volatiles were removed in vacuo was extracted with ethyl acetate (3×15 mL) The organics were separated the combined organics were washed with brine solution dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromopropane (3.39 mL, 36.2 mmol) was added to a suspension of 4-bromo-2-methoxy-phenol (5 g, 24.1 mmol), K2CO3 (6.67 g, 48.3 mmol) and DMSO (71 mL) at room temperature. The heterogeneous mixture was stirred at 55° C. for 2 hours, then cooled to room temperature and diluted with water. The reaction mixture was extracted with Et2O and the extract was washed successively with 10% aq. NaOH solution, water, then brine solution. The organics were separated and dried over sodium sulfate, filtered and concentrated in vacuo to give 4-bromo-1-isopropoxy-2-methoxy-benzene (5.83 g, 94%) as a pale yellow oil. ESI-MS m/z calc. 244.0. Found 245.0 (M+1)+; Retention time: 1.93 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.03-6.95 (m, 2H), 6.76 (dd, J=7.7, 1.1 Hz, 1H), 4.47 (dt, J=12.2, 6.1 Hz, 1H), 3.84 (s, 3H), 1.35 (d, J=6.1 Hz, 6H). cooled to room temperature The reaction mixture was extracted with Et2O the extract was washed successively with 10% aq. NaOH solution, water The organics were separated dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under an atmosphere of nitrogen, tert-butyllithium (2.14 mL of 1.6 M in toluene, 3.42 mmol) was added dropwise to a solution of 4-bromo-1-isopropoxy-2-methoxy-benzene (400 mg, 1.63 mmol) in THF (6 mL) at −78° C. The reaction mixture was allowed to stir for 1 hour at −78° C., then added dropwise to a flask containing CO2 (1.8 g, 40.8 mmol) (solid, dry ice) in THF (2 mL). The reaction mixture was allowed to stir for 30 minutes warming to room temperature. Water (20 mL) was added to the reaction mixture and the volatiles were removed in vacuo. The resultant aqueous layer was acidified with 1N HCl solution to pH 1 and was extracted with ethyl acetate (3×15 mL). The organics were separated and the combined organics were washed with brine solution, dried over sodium sulfate, filtered and concentrated in vacuo to give 4-isopropoxy-3-methoxy-benzoic acid (310 mg, 85%) as a white solid. ESI-MS m/z calc. 210.1, found 211.1 (M+1)+; Retention time: 1.23 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 12.63 (s, 1H), 7.53 (dd, J=8.4, 2.0 Hz, 1H), 7.44 (d, J=2.0 Hz, 1H), 7.04 (d, J=8.7 Hz, 1H), 4.67 (dt, J=12.1, 6.0 Hz, 1H), 3.78 (s, 3H), 1.28 (d, J=6.0 Hz, 6H). added dropwise to a flask to stir for 30 minutes warming to room temperature the volatiles were removed in vacuo was extracted with ethyl acetate (3×15 mL) The organics were separated the combined organics were washed with brine solution dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromopropane (3.39 mL, 36.2 mmol) was added to a suspension of 4-bromo-2-methoxy-phenol (5 g, 24.1 mmol), K2CO3 (6.67 g, 48.3 mmol) and DMSO (71 mL) at room temperature. The heterogeneous mixture was stirred at 55° C. for 2 hours, then cooled to room temperature and diluted with water. The reaction mixture was extracted with Et2O and the extract was washed successively with 10% aq. NaOH solution, water, then brine solution. The organics were separated and dried over sodium sulfate, filtered and concentrated in vacuo to give 4-bromo-1-isopropoxy-2-methoxy-benzene (5.83 g, 94%) as a pale yellow oil. ESI-MS m/z calc. 244.0, found 245.0 (M+1)+; Retention time: 1.93 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.03-6.95 (m, 2H), 6.76 (dd, J=7.7, 1.1 Hz, 1H), 4.47 (dt, J=12.2, 6.1 Hz, 1H), 3.84 (s, 3H), 1.35 (d, J=6.1 Hz, 6H). cooled to room temperature The reaction mixture was extracted with Et2O the extract was washed successively with 10% aq. NaOH solution, water The organics were separated dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under a balloon of N2, tert-butyllithium (2.14 mL of 1.6 M, 3.43 mmol) was added drop-wise to a solution of 4-bromo-1-isopropoxy-2-methoxy-benzene (400 mg, 1.63 mmol) in THF (6.0 mL) at −78° C. The mixture was allowed to stir for 1 h at −78° C. before it was added drop-wise to a flask containing CO2 (1.80 g, 40.8 mmol)(solid, dry ice) in THF (2.0 mL). The mixture was allowed to stir for 30 min as it warmed to room temperature (caution: CO2 gas evolution). Water (20 mL) was added and the volatiles were removed under reduced pressure. The resultant aqueous layer was acidified with 1N HCl to pH ˜1-2 and the mixture was extracted with ethyl acetate (3×15 mL). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated to give 4-isopropoxy-3-methoxy-benzoic acid (≧94% pure, 310 mg, 85%) as a white solid. ESI-MS m/z calc. 210.1, found 210.9 (M+1)+; Retention time: 1.23 min. 1H NMR (400 MHz, DMSO) δ 12.63 (s, 1H), 7.53 (dd, J=8.4, 2.0 Hz, 1H), 7.44 (d, J=2.0 Hz, 1H), 7.04 (d, J=8.7 Hz, 1H), 4.67 (dt, J=12.1, 6.0 Hz, 1H), 3.78 (s, 3H), 1.28 (d, J=6.0 Hz, 6H). was added drop-wise to a flask to stir for 30 min as it the volatiles were removed under reduced pressure the mixture was extracted with ethyl acetate (3×15 mL) The combined organics were washed with brine dried over sodium sulfate filtered concentrated

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under an atmosphere of nitrogen, tert-butyllithium (2.14 mL of 1.6 M in toluene, 3.42 mmol) was added dropwise to a solution of 4-bromo-1-isopropoxy-2-methoxy-benzene (400 mg, 1.63 mmol) in THF (6 mL) at −78° C. The reaction mixture was allowed to stir for 1 hour at −78° C., then added dropwise to a flask containing CO2 (1.8 g, 40.8 mmol) (solid, dry ice) in THF (2 mL). The reaction mixture was allowed to stir for 30 minutes warming to room temperature. Water (20 mL) was added to the reaction mixture and the volatiles were removed in vacuo. The resultant aqueous layer was acidified with 1N HCl solution to pH 1 and was extracted with ethyl acetate (3×15 mL). The organics were separated and the combined organics were washed with brine solution, dried over sodium sulfate, filtered and concentrated in vacuo to give 4-isopropoxy-3-methoxy-benzoic acid (310 mg, 85%) as a white solid. ESI-MS m/z calc. 210.1. found 211.1 (M+1)+; Retention time: 1.23 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 12.63 (s, 1H), 7.53 (dd, J=8.4, 2.0 Hz, 1H), 7.44 (d, J=2.0 Hz, 1H), 7.04 (d, J=8.7 Hz, 1H), 4.67 (dt, J=12.1, 6.0 Hz, 1H), 3.78 (s, 3H), 1.28 (d, J=6.0 Hz, 6H). added dropwise to a flask to stir for 30 minutes warming to room temperature the volatiles were removed in vacuo was extracted with ethyl acetate (3×15 mL) The organics were separated the combined organics were washed with brine solution dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromopropane (3.39 mL, 36.2 mmol) was added to a suspension of 4-bromo-2-methoxy-phenol (5 g, 24.1 mmol), K2CO3 (6.67 g, 48.3 mmol) and DMSO (71 mL) at room temperature. The heterogeneous mixture was stirred at 55° C. for 2 hours, then cooled to room temperature and diluted with water. The reaction mixture was extracted with Et2O and the extract was washed successively with 10% aq. NaOH solution, water, then brine solution. The organics were separated and dried over sodium sulfate, filtered and concentrated in vacuo to give 4-bromo-1-isopropoxy-2-methoxy-benzene (5.83 g, 94%) as a pale yellow oil. ESI-MS m/z calc. 244.0. found 245.0 (M+1)+; Retention time: 1.93 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.03-6.95 (m, 2H), 6.76 (dd, J=7.7, 1.1 Hz, 1H), 4.47 (dt, J=12.2, 6.1 Hz, 1H), 3.84 (s, 3H), 1.35 (d, J=6.1 Hz, 6H). cooled to room temperature The reaction mixture was extracted with Et2O the extract was washed successively with 10% aq. NaOH solution, water The organics were separated dried over sodium sulfate filtered concentrated in vacuo