4-溴-3-羟基苯甲酸乙酯

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

实验步骤: To a suspension of 4.5 g (18.4 mmol) of 6 and 4.1 g (30 mmol) of K2CO3 in 150 ml of acetone under Ar was added 3.4 g (20 mmol) of BnBr. The mixture was heated at reflux for 15 h, concentrated, then diluted with 100 ml of CH2Cl2, washed (water, 1 N HCl, and brine), and dried (Na2SO4). Concentration and chromatography (EtOAc/hexane) afforded 5.2 g (84%) of 7 (white solid): 1H NMR (300 MHz, CDCl3) δ 1.39 (t, J=7.2 Hz, 3 H), 4.37 (q, J=7.2 Hz, 2 H), 5.21 (s, 2 H), 7.39 (m, 3 H), 7.50 (in, 3 H), 7.63 ppm (m, 2 H). The mixture was heated at reflux for 15 h concentrated diluted with 100 ml of CH2Cl2 washed (water, 1 N HCl, and brine) dried (Na2SO4) Concentration and chromatography (EtOAc/hexane)

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

实验步骤: To a mixture containing 4-bromo-3-hydroxybenzoic acid (5.0 g, 0.023 mol) and 5 ml of EtOH in 150 ml of benzene was added 1 ml of MeSO3H. The mixture was heated at reflux for 10 h using a Dean-Stark trap to collect water, then concentrated. The residue was dissolved in CH2Cl2, washed (water, 5% NaHCO3, and brine), dried (Na2SO4), and concentrated. The crude product was chromatographed (EtOAc/hexane) to gave a white solid (5.1 g, 90%): 1H NMR (300 MHz, CDCl3) δ 1.39 (t, J=7.2 Hz, 3 H), 4.37 (q, J=7.2 Hz, 2 H), 5.75 (s, 1 H), 7.48 (d, J=8.1 Hz, 1 H), 7.55 (d, J=8.1 Hz, 1 H), 7.68 ppm (s, 1 H). The mixture was heated at reflux for 10 h to collect water concentrated The residue was dissolved in CH2Cl2 washed (water, 5% NaHCO3, and brine) dried (Na2SO4) concentrated The crude product was chromatographed (EtOAc/hexane)

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

实验步骤: To a mixture containing 4-bromo-3-hydroxybenzoic acid (5.0 g, 0.023 mol) and 5 ml of EtOH in 150 ml of benzene was added 1 ml of MeSO3H. The mixture was heated at reflux for 10 h using a Dean-Stark trap to collect water, then concentrated. The residue was dissolved in CH2Cl2, washed (water, 5% NaHCO3, and brine), dried (Na2SO4), and concentrated. The crude product was chromatographed (EtOAc/hexane) to gave a white solid (5.1 g, 90%): 1H NMR (300 MHz, CDCl3) δ 1.39 (t, J=7.2 Hz, 3 H), 4.37 (q, J=7.2 Hz, 2 H), 5.75 (s, 1 H), 7.48 (d, J=8.1 Hz, 1 H), 7.55 (d, J=8.1 Hz, 1 H), 7.68 ppm (s, 1 H). The mixture was heated at reflux for 10 h to collect water concentrated The residue was dissolved in CH2Cl2 washed (water, 5% NaHCO3, and brine) dried (Na2SO4) concentrated The crude product was chromatographed (EtOAc/hexane)

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

实验步骤: Ethyl 4-bromo-3-hydroxybenzoate (2.0 g, 8.2 mmol), potassium carbonate (3.4 g, 24.48 mmol and (chloromethyl)cyclopropane (1.13 mL, 12.24 mmol) were placed in 50 mL DMF and the reaction was heated at 80° C. for 18 h. The mixture was cooled and partitioned between EtOAc and water. The organic layer was separated, washed with water, brine, dried (Na2SO4), filtered, and the filtrate was concentrated to an oil. Purification by column chromatography on silica gel using 0-50% EtOAc/hexane gave the product (0.77 g, 31%) as a clear oil. The mixture was cooled partitioned between EtOAc and water The organic layer was separated washed with water, brine dried (Na2SO4) filtered the filtrate was concentrated to an oil Purification by column chromatography on silica gel using 0-50% EtOAc/hexane

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

实验步骤: Ethyl 4-bromo-3-hydroxybenzoate (1.5 g, 6.12 mmol), potassium carbonate (5.07 g, 36.72 mmol) and 1-chloro-2-methylpropan-2-ol (0.75 mL, 7.34 mmol) were placed in 50 mL DMF and the reaction was heated at 80° C. for 18 h. The mixture was cooled and partitioned between EtOAc and water. The organic layer was separated, washed with water, brine, dried (Na2SO4), filtered, and the filtrate was concentrated under vacuum to an oil. Purification by column chromatography on silica gel using EtOAc/hexane (0-50%) gave the product (0.5 g, 26%) as a yellow oil. The mixture was cooled partitioned between EtOAc and water The organic layer was separated washed with water, brine dried (Na2SO4) filtered the filtrate was concentrated under vacuum to an oil Purification by column chromatography on silica gel

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

实验步骤: Ethyl 4-bromo-3-hydroxybenzoate (prepared according to M. I. Dawson et al WO 2003048101; 0.5 g, 2.04 mmol), potassium carbonate (0.84 g, 6.12 mmol) and iodoethane (0.2 mL, 2.45 mmol) were placed in 50 mL DMF and the reaction was heated at 80° C. for 18 h. The mixture was cooled and partitioned between EtOAc and water. The organic layer was separated, washed with water, brine, dried (Na2SO4), filtered, and the filtrate was concentrated under vacuum to an oil. The oil was purified by column chromatography using EtOAc/hexane (0-50%) as eluent to give the product (0.35 g, 62%) as a clear oil. The mixture was cooled partitioned between EtOAc and water The organic layer was separated washed with water, brine dried (Na2SO4) filtered the filtrate was concentrated under vacuum to an oil The oil was purified by column chromatography

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

实验步骤: Ethyl 4-bromo-3-hydroxybenzoate (1.5 g, 6.12 mmol), potassium carbonate (2.5 g, 18.37 mmol) and 4-(2-chloroethyl)morpholine hydrochloride (1.4 g, 7.35 mmol) were placed in 50 mL DMF and the reaction was heated at 80° C. for 18 h. The mixture was cooled and partitioned between EtOAc and water. The organic layer was separated, washed with water, brine, dried (Na2SO4), filtered, and the filtrate was concentrated to an oil. Purification by column chromatography on silica gel using 0-50% EtOAc/hexane as eluent gave the product (1.0 g, 47%) as a colorless oil. The mixture was cooled partitioned between EtOAc and water The organic layer was separated washed with water, brine dried (Na2SO4) filtered the filtrate was concentrated to an oil Purification by column chromatography on silica gel using 0-50% EtOAc/hexane as eluent

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

实验步骤: Ethyl 4-bromo-3-hydroxybenzoate (200 mg) was dissolved in DMF (10 ml) and 4-iodo-butyl acetate (195 μl) and sodium hydride (56 mg, 60% dispersion in mineral oil) were added and the reaction stirred at 80° C. under nitrogen for 3 hours. The reaction was quenched with water (5 ml) and the solvents evaporated under vacuum. The residue was partitioned between ethyl acetate/chloroform (1:1) and water. The organic phase was dried using a hydrophobic filter and the solvent evaporated in vacuo to give ethyl 3-{[4-(acetyloxy)butyl]oxy}-4-bromobenzoate as a yellow gel (318 mg). The reaction was quenched with water (5 ml) the solvents evaporated under vacuum The residue was partitioned between ethyl acetate/chloroform (1:1) and water The organic phase was dried a hydrophobic filter the solvent evaporated in vacuo

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

实验步骤: 4-Bromo-3-hydroxybenzoic acid (100 mg) was dissolved in absolute ethanol (10 ml) and concentrated sulfuric acid (60 μl) added. The reaction was heated at reflux under nitrogen for 22 hours. The solvent was evaporated and the residue was partitioned between ethyl acetate/chloroform (1:1) and water. The organic layers were combined, dried using a hydrophobic filter and the solvent evaporated leaving ethyl 4-bromo-3-hydroxybenzoate as a white solid (109 mg). The reaction was heated at reflux under nitrogen for 22 hours The solvent was evaporated the residue was partitioned between ethyl acetate/chloroform (1:1) and water dried a hydrophobic filter the solvent evaporated

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

实验步骤: To a suspension of 4.5 g (18.4 mmol) of 6 and 4.1 g (30 mmol) of K2CO3 in 150 ml of acetone under Ar was added 3.4 g (20 mmol) of BnBr. The mixture was heated at reflux for 15 h, concentrated, then diluted with 100 ml of CH2Cl2, washed (water, 1 N HCl, and brine), and dried (Na2SO4). Concentration and chromatography (EtOAc/hexane) afforded 5.2 g (84%) of 7 (white solid): 1H NMR (300 MHz, CDCl3) δ 1.39 (t, J=7.2 Hz, 3 H), 4.37 (q, J=7.2 Hz, 2 H), 5.21 (s, 2 H), 7.39 (m, 3 H), 7.50 (in, 3 H), 7.63 ppm (m, 2 H). The mixture was heated at reflux for 15 h concentrated diluted with 100 ml of CH2Cl2 washed (water, 1 N HCl, and brine) dried (Na2SO4) Concentration and chromatography (EtOAc/hexane)

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

实验步骤: To a mixture containing 4-bromo-3-hydroxybenzoic acid (5.0 g, 0.023 mol) and 5 ml of EtOH in 150 ml of benzene was added 1 ml of MeSO3H. The mixture was heated at reflux for 10 h using a Dean-Stark trap to collect water, then concentrated. The residue was dissolved in CH2Cl2, washed (water, 5% NaHCO3, and brine), dried (Na2SO4), and concentrated. The crude product was chromatographed (EtOAc/hexane) to gave a white solid (5.1 g, 90%): 1H NMR (300 MHz, CDCl3) δ 1.39 (t, J=7.2 Hz, 3 H), 4.37 (q, J=7.2 Hz, 2 H), 5.75 (s, 1 H), 7.48 (d, J=8.1 Hz, 1 H), 7.55 (d, J=8.1 Hz, 1 H), 7.68 ppm (s, 1 H). The mixture was heated at reflux for 10 h to collect water concentrated The residue was dissolved in CH2Cl2 washed (water, 5% NaHCO3, and brine) dried (Na2SO4) concentrated The crude product was chromatographed (EtOAc/hexane)

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

实验步骤: To a suspension of 4.5 g (18.4 mmol) of 6 and 4.1 g (30 mmol) of K2CO3 in 150 ml of acetone under Ar was added 3.4 g (20 mmol) of BnBr. The mixture was heated at reflux for 15 h, concentrated, then diluted with 100 ml of CH2Cl2, washed (water, 1 N HCl, and brine), and dried (Na2SO4). Concentration and chromatography (EtOAc/hexane) afforded 5.2 g (84%) of 7 (white solid): 1H NMR (300 MHz, CDCl3) δ 1.39 (t, J=7.2 Hz, 3 H), 4.37 (q, J=7.2 Hz, 2 H), 5.21 (s, 2 H), 7.39 (m, 3 H), 7.50 (in, 3 H), 7.63 ppm (m, 2 H). The mixture was heated at reflux for 15 h concentrated diluted with 100 ml of CH2Cl2 washed (water, 1 N HCl, and brine) dried (Na2SO4) Concentration and chromatography (EtOAc/hexane)