2-溴-4-(甲基磺酰基)苯酚

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-bromo-4-methanesulfonylphenol (7.2 g, 29 mmol), (chloromethyl)cyclopropane (4.3 g, 32 mmol) and K2CO3 (8 g, 58 mmol) in acetone (80 mL) was stirred at 80° C. for 5 h. The mixture was quenched with water (40 mL). Extractive work up with ethyl acetate and purification by preparative HPLC gave the title compound (2.5 g, 28.6%). 1H NMR (CDCl3, 400 MHz) δ 8.12 (d, J=2.3 Hz, 1H), 7.84 (dd, J1=2.3 Hz, J2=8.7 Hz, 1H), 6.97 (d, J=8.8 Hz, 1H), 3.99 (d, J=6.7 Hz, 2H), 3.05 (s, 3H), 1.23-1.43 (m, 1H), 0.70 (d, J=7.9 Hz, 2H), 0.44 (d, J=5.4 Hz, 2H). The mixture was quenched with water (40 mL) Extractive work up with ethyl acetate and purification by preparative HPLC

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-bromo-4-methanesulfonylphenol (7.2 g, 29 mmol), (chloromethyl)cyclopropane (4.3 g, 32 mmol) and K2CO3 (8 g, 58 mmol) in acetone (80 mL) was stirred at 80° C. for 5 h. The mixture was quenched with water (40 mL). Extractive work up with ethyl acetate and purification by preparative HPLC gave the title compound (2.5 g, 28.6%). 1H NMR (CDCl3, 400 MHz) δ 8.12 (d, J=2.3 Hz, 1H), 7.84 (dd, J1=2.3 Hz, J2=8.7 Hz, 1H), 6.97 (d, J=8.8 Hz, 1H), 3.99 (d, J=6.7 Hz, 2H), 3.05 (s, 3H), 1.23-1.43 (m, 1H), 0.70 (d, J=7.9 Hz, 2H), 0.44 (d, J=5.4 Hz, 2H). The mixture was quenched with water (40 mL) Extractive work up with ethyl acetate and purification by preparative HPLC

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-bromo-4-(methylsulfonyl)phenol (3.2 g, 12.7 mmol) in DMF (35 mL) at 0° C. was added K2CO3 (5.3 g, 38.1 mmol). The reaction was stirred at 0° C. for 0.5 h and to this cold solution was slowly added CH3I (2.7 g, 19.1 mmol) drop wise. The reaction was stirred at r.t. overnight. After the reaction was completed, 80 mL of ice-water was added. The mixture was extracted with EA (60 mL×3). The combined organic layers were washed with brine and dried over Na2SO4. After filtration and evaporation of the solvent, the obtained residue was purified on column chromatography (silica gel, ethyl acetate/petroleum ether=1:4) to give 2-bromo-1-methoxy-4-(methylsulfonyl)benzene (2.12 g, 63.0%) as yellow solid. The reaction was stirred at r.t. overnight The mixture was extracted with EA (60 mL×3) The combined organic layers were washed with brine dried over Na2SO4 After filtration and evaporation of the solvent the obtained residue was purified on column chromatography (silica gel, ethyl acetate/petroleum ether=1:4)

反应条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-(methylsulfonyl)phenol (5 g, 29.1 mmol) in ether (100 mL) at −15° C. was slowly added acetic acid (5 mL). To this cold solution was slowly added Br2 (5.1 g, 32.0 mmol) and the reaction was stirred at −10° C. for 1 h and then warmed to r.t. and stirred for further 10 h. After the reaction was completed, 100 mL of sat. NaHCO3 aq. was added and the mixture was extracted with EA (50 mL×3). The combined organic layers were washed with brine and dried over Na2SO4. After filtration and evaporation of the solvent, 2-bromo-4-(methylsulfonyl)phenol (3.2 g, 43.6%) was obtained as a white solid. at −15° C. warmed to r.t. stirred for further 10 h the mixture was extracted with EA (50 mL×3) The combined organic layers were washed with brine dried over Na2SO4 After filtration and evaporation of the solvent

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-bromo-4-(methylsulfonyl) phenol (3.2 g, 12.7 mmol) in DMF (35 mL) at 0° C. was added K2CO3 (5.3 g, 38.1 mmol). The reaction was stirred at 0° C. for 0.5 h and to this cold solution was slowly added CH3I (2.7 g, 19.1 mmol) drop wise. The reaction was stirred at r.t. overnight. After the reaction was completed, 80 mL of ice-water was added. The mixture was extracted with EA (60 mL×3). The combined organic layers were washed with brine and dried over Na2SO4. After filtration and evaporation of the solvent, the obtained residue was purified on column chromatography (silica gel, ethyl acetate/petroleum ether=1:4) to give 2-bromo-1-methoxy-4-(methylsulfonyl)benzene (2.12 g, 63.0%) as yellow solid. The reaction was stirred at r.t. overnight The mixture was extracted with EA (60 mL×3) The combined organic layers were washed with brine dried over Na2SO4 After filtration and evaporation of the solvent the obtained residue was purified on column chromatography (silica gel, ethyl acetate/petroleum ether=1:4)

反应条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-(methylsulfonyl)phenol (5 g, 29.1 mmol) in ether (100 mL) at −15° C. was slowly added acetic acid (5 mL). To this cold solution was slowly added Br2 (5.1 g, 32.0 mmol) and the reaction was stirred at −10° C. for 1 h and then warmed to r.t. and stirred for further 10 h. After the reaction was completed, 100 mL of sat. NaHCO3 aq. was added and the mixture was extracted with EA (50 mL×3). The combined organic layers were washed with brine and dried over Na2SO4. After filtration and evaporation of the solvent, 2-bromo-4-(methylsulfonyl)phenol (3.2 g, 43.6%) was obtained as a white solid. at −15° C. warmed to r.t. stirred for further 10 h the mixture was extracted with EA (50 mL×3) The combined organic layers were washed with brine dried over Na2SO4 After filtration and evaporation of the solvent

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Potassium carbonate (2.31 g, 16.8 mmol) was added to a solution of 2-bromo-4-(methanesulfonyl)phenol (Description 27; 3.5 g, 14 mmol) in dimethylformamide (50 ml). The resulting solution was stirred for 30 min. and methyl iodide (1.04 ml, 16.8 mmol). After stirring for 1 h. the solution was poured into water (200 ml) and extracted with ethyl acetate (2×100 ml). The combined organics were washed with water and dried over sodium sulphate. Removal of the solvent in vacuo gave a white solid which was crystallised from diethyl ether to give the title compound (2.02 g). 1H NMR (250 MHz, CDCl3) δ8.12-8.11 (1H, d, J 2.2 Hz), 7.90-7.86 (1H, dd, J 8.7, 2.2 Hz), 7.04-7.00 (1H, d, J 8.7 Hz), and 3.99 (3H, s), and 3.05 (3H, s). After stirring for 1 h. the solution extracted with ethyl acetate (2×100 ml) The combined organics were washed with water dried over sodium sulphate Removal of the solvent in vacuo gave a white solid which was crystallised from diethyl ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of bromine (0.9 ml, 17.45 mmol) in glacial acetic acid (10 ml) was added dropwise to a stirred solution of 4-(methanesulfonyl)phenol (Description 26; 3 g, 17.45 mmol). The resulting solution was stirred at ambient temperature for 16 h. Bromine (0.45 ml) in glacial acetic acid (5 ml) was added dropwise and the solution was stirred for 2 h. The excess acetic acid and bromine were removed in vacuo and the residue was azeotroped with toluene to give the desired compound as an off-white solid (3.54 g, 81%). 1H NMR (250 MHz, CDCl3) δ8.06-8.05 (1H, d, J 2.3 Hz), 7.73-7.69 (1H, dd, J 8.6, 2.3 Hz), 7.06-7.02 (1H, d, J 8.6 Hz), and 3.06 (3H, s). the solution was stirred for 2 h The excess acetic acid and bromine were removed in vacuo the residue was azeotroped with toluene

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-bromo-4-(methylsulfonyl)phenol (243 mg, 0.968 mmol) and K2CO3 (201 mg, 1.45 mmol) in DMF (2 mL) was added CH3I (0.0660 mL, 1.06 mmol). The reaction was stirred at room temperature for overnight, diluted reaction with EtOAc (10 mL) and water (10 mL). The organic layer was separated, and the aqueous layer extracted again with EtOAc (15 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, concentrated, and purified with a silica gel column by ISCO CombiFlash® chromatography eluting with 10%-40% EtOAc/Heptane to afford the desired product (168 mg, 65.5%) as a white solid. diluted The organic layer was separated the aqueous layer extracted again with EtOAc (15 mL) The combined organic layers were washed with brine dried over sodium sulfate filtered concentrated purified with a silica gel column by ISCO CombiFlash® chromatography eluting with 10%-40% EtOAc/Heptane

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-bromo-4-methanesulfonylphenol (7.2 g, 29 mmol), (chloromethyl)cyclopropane (4.3 g, 32 mmol) and K2CO3 (8 g, 58 mmol) in acetone (80 mL) was stirred at 80° C. for 5 h. The mixture was quenched with water (40 mL). Extractive work up with ethyl acetate and purification by preparative HPLC gave the title compound (2.5 g, 28.6%). 1H NMR (CDCl3, 400 MHz) δ 8.12 (d, J=2.3 Hz, 1H), 7.84 (dd, J1=2.3 Hz, J2=8.7 Hz, 1H), 6.97 (d, J=8.8 Hz, 1H), 3.99 (d, J=6.7 Hz, 2H), 3.05 (s, 3H), 1.23-1.43 (m, 1H), 0.70 (d, J=7.9 Hz, 2H), 0.44 (d, J=5.4 Hz, 2H). The mixture was quenched with water (40 mL) Extractive work up with ethyl acetate and purification by preparative HPLC