4-溴-2-氟-1-((2-甲氧基乙氧基)甲基)苯

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Methoxyethanol (5.0 g) was added to a stirred suspension of sodium hydride (2.64 g of a 60% mineral oil suspension) in DHF (200 ml) at room temperature and under a atmosphere of argon. The stirred mixture was heated to 60° C. and then cooled to 5° C. A solution of 4-bromo-2-fluorobenzyl bromide (15 g) in dichlorobenzene (75 ml) was added over 15 minutes. The mixture stirred for 12 hours at room temperature, then for 1 hour at 60° C. and cooled. The mixture was diluted with iced water (600 ml) and extracted with ethyl acetate (3×200 ml). The combined extracts were washed with 2M hydrochloric acid (100 ml), water (2×100 ml), saturated brine (100 ml) and dried (MgSO4). Evaporation of the solvents gave an oil which was distilled using a short path distillation apparatus to give 1-(4-bromo-2-fluorobenzyloxy)-2-methyoxyethane (11.6 g), furnace temperature 125° C./0.01 bar; NMR (CDCl3): 3.40(3H, s), 3.5-3.7(4H, m), 4.58(2H, s) and 7.2-7.4(3H, m). cooled to 5° C for 1 hour at 60° C. cooled extracted with ethyl acetate (3×200 ml) The combined extracts were washed with 2M hydrochloric acid (100 ml), water (2×100 ml), saturated brine (100 ml) dried (MgSO4) Evaporation of the solvents gave an oil which was distilled a short path distillation apparatus

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of (4-bromo-2-fluorophenyl)methanol (10 g, 49.02 mmol) in THF (250 mL) at 0° C., was added 60% NaH (2.93 g, 73.53 mmol) slowly in portions. After addition, the suspension was heated to 5° C. for 30 min, cooled to RT, then was added 1-bromo-2-methoxy ethane (5 mL, 53.92 mmol) and the mixture was stirred at RT for 20 h until complete consumption of (4-bromo-2-fluorophenyl)methanol, as evidenced by TLC analysis. The reaction mixture was diluted with ice cold water (100 mL) and concentrated under reduced pressure. The obtained aqueous residue was extracted with EtOAc (2×150 mL); the combined EtOAc layers were washed with brine solution (50 mL), dried over anhydrous NaSO4, filtered and concentrated. The obtained crude compound was purified by CC using 5% EtOAc in PE as eluent to afford 4-bromo-2-fluoro-1-((2-methoxyethoxy)methyl)benzene (6 g, 47%) as yellow liquid (TLC solvent system: 30% EtOAc-PE; Rf: 0.4). After addition cooled to RT concentrated under reduced pressure The obtained aqueous residue was extracted with EtOAc (2×150 mL) the combined EtOAc layers were washed with brine solution (50 mL) dried over anhydrous NaSO4 filtered concentrated The obtained crude compound was purified by CC

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Methoxyethanol (5.0 g) was added to a stirred suspension of sodium hydride (2.64 g of a 60% mineral oil suspension) in DHF (200 ml) at room temperature and under a atmosphere of argon. The stirred mixture was heated to 60° C. and then cooled to 5° C. A solution of 4-bromo-2-fluorobenzyl bromide (15 g) in dichlorobenzene (75 ml) was added over 15 minutes. The mixture stirred for 12 hours at room temperature, then for 1 hour at 60° C. and cooled. The mixture was diluted with iced water (600 ml) and extracted with ethyl acetate (3×200 ml). The combined extracts were washed with 2M hydrochloric acid (100 ml), water (2×100 ml), saturated brine (100 ml) and dried (MgSO4). Evaporation of the solvents gave an oil which was distilled using a short path distillation apparatus to give 1-(4-bromo-2-fluorobenzyloxy)-2-methyoxyethane (11.6 g), furnace temperature 125° C./0.01 bar; NMR (CDCl3): 3.40(3H, s), 3.5-3.7(4H, m), 4.58(2H, s) and 7.2-7.4(3H, m). cooled to 5° C for 1 hour at 60° C. cooled extracted with ethyl acetate (3×200 ml) The combined extracts were washed with 2M hydrochloric acid (100 ml), water (2×100 ml), saturated brine (100 ml) dried (MgSO4) Evaporation of the solvents gave an oil which was distilled a short path distillation apparatus