3-bromo-5-methoxyphenol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Bromo-5-methoxyphenol (7.60 g, 37.4 mmol) synthesized in Example (78a) was dissolved in toluene (100 mL), and R-(−)-1-methoxy-2-propanol (4.40 mL, 44.9 mmol) and triphenylphosphine (13.8 g, 52.6 mmol) were added, followed by dropwise addition of diethyl azodicarboxylate (2.2 mol/l toluene solution, 24 mL, 52.8 mmol) at 0° C. and stirring at room temperature for 1.5 hours under nitrogen atmosphere. The solvent was distilled off under reduced pressure, diethyl ether (100 mL) was added, and the deposit was filtered to be removed. The mother liquor was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=10%-20%) to afford the desired compound (9.22 g, yield 89%) as a colorless liquid. The solvent was distilled off under reduced pressure, diethyl ether (100 mL) was added the deposit was filtered to be removed The mother liquor was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=10%-20%)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available 1-bromo-3,5-dimethoxybenzene (18.74 g, 86.3 mmol) was dissolved in 1-methyl-2-pyrrolidone (100 mL), and sodium thiomethoxide (6.74 g, 96.2 mmol) was added, followed by stirring at 100° C. for 3 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, 1N hydrochloric acid (200 mL) was added, and extraction was carried out with diethyl ether (500 mL). The organic layer was washed with saturated brine, and subsequently dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=20%-25%) to afford the desired compound (15.03 g, yield 86%) as a white solid. The reaction solution was cooled to room temperature extraction The organic layer was washed with saturated brine subsequently dried over sodium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=20%-25%)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available 1-bromo-3,5-dimethoxybenzene (18.74 g, 86.3 mmol) was dissolved in 1-methyl-2-pyrrolidone (100 mL), and sodium thiomethoxide (6.74 g, 96.2 mmol) was added, followed by stirring at 100° C. for 3 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, 1N hydrochloric acid (200 mL) was added, and extraction was carried out with diethyl ether (500 mL). The organic layer was washed with saturated brine, and subsequently dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=20%-25%) to afford the desired compound (15.03 g, yield 86%) as a white solid. The reaction solution was cooled to room temperature extraction The organic layer was washed with saturated brine subsequently dried over sodium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=20%-25%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Bromo-5-methoxyphenol (7.60 g, 37.4 mmol) synthesized in Example (1a) was dissolved in toluene (100 mL), and R-(−)-1-methoxy-2-propanol (4.40 mL, 44.9 mmol) and triphenylphosphine (13.8 g, 52.6 mmol) were added, followed by dropwise addition of diethyl azodicarboxylate (2.2 mol/l toluene solution, 24 mL, 52.8 mmol) at 0° C. and stirring at room temperature for 1.5 hours under nitrogen atmosphere. The solvent was distilled off under reduced pressure, diethyl ether (100 mL) was added, and the deposit was filtered to be removed. The mother liquor was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=10%-20%) to afford the desired compound (9.22 g, yield 89%) as a colorless liquid. The solvent was distilled off under reduced pressure, diethyl ether (100 mL) was added the deposit was filtered to be removed The mother liquor was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=10%-20%)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available 1-bromo-3,5-dimethoxybenzene (18.74 g, 86.3 mmol) was dissolved in 1-methyl-2-pyrrolidone (100 mL), and sodium thiomethoxide (6.74 g, 96.2 mmol) was added, followed by stirring at 100° C. for 3 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, 1N hydrochloric acid (200 mL) was added, and extraction was carried out with diethyl ether (500 mL). The organic layer was washed with saturated brine, and subsequently dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=20%-25%) to afford the desired compound (15.03 g, yield 86%) as a white solid. The reaction solution was cooled to room temperature extraction The organic layer was washed with saturated brine subsequently dried over sodium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=20%-25%)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available 1-bromo-3,5-dimethoxybenzene (18.74 g, 86.3 mmol) was dissolved in 1-methyl-2-pyrrolidone (100 mL), and sodium thiomethoxide (6.74 g, 96.2 mmol) was added, followed by stirring at 100° C. for 3 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, 1N hydrochloric acid (200 mL) was added, and extraction was carried out with diethyl ether (500 mL). The organic layer was washed with saturated brine, and subsequently dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=20%-25%) to afford the desired compound (15.03 g, yield 86%) as a white solid. The reaction solution was cooled to room temperature extraction The organic layer was washed with saturated brine subsequently dried over sodium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=20%-25%)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-bromo-3,5-dimethyoxybenzene (3.0 g, 13.8 mmol) was dissolved in dichloromethane (45 mL) and the solution was cooled to −78° C. Boron tribromide (1M in dichloromethane, 41 mL, 41 mmol) was added and the solution was warmed gradually to room temperature over 18 hours. After cooling to −78° C., the reaction was quenched with water (100 mL). The organics were separated and washed with sodium thiosulphate solution then water, then dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with pentane:ethyl acetate 100:0 to 80:20, to afford the title compound in 16% yield (470 mg). the solution was warmed gradually to room temperature over 18 hours After cooling to −78° C. the reaction was quenched with water (100 mL) The organics were separated washed with sodium thiosulphate solution water, then dried over magnesium sulfate concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with pentane:ethyl acetate 100:0 to 80:20

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-bromo-3,5-dimethyoxybenzene (3.0 g, 13.8 mmol) was dissolved in dichloromethane (45 mL) and the solution was cooled to −78° C. Boron tribromide (1M in dichloromethane, 41 mL, 41 mmol) was added and the solution was warmed gradually to room temperature over 18 hours. After cooling to −78° C., the reaction was quenched with water (100 mL). The organics were separated and washed with sodium thiosulphate solution then water, then dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with pentane:ethyl acetate 100:0 to 80:20, to afford the title compound in 16% yield (470 mg). the solution was warmed gradually to room temperature over 18 hours After cooling to −78° C. the reaction was quenched with water (100 mL) The organics were separated washed with sodium thiosulphate solution water, then dried over magnesium sulfate concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with pentane:ethyl acetate 100:0 to 80:20

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Bromo-5-methoxyphenol (0.18 g, 0.89 mmol) and triphenylphosphine (0.284, 1.07 mmol) were taken into THF (5 mL) and the resulting mixture cooled to 0° C. 4-Hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.18 g, 0.89 mmol), and DIAD (0.207 mL, 1.07 mmol) were taken up into THF (5 mL) and added slowly to the mixture, which was then stirred at room temperature over night. The resulting mixture was taken into EtOAc and washed with saturated NaHCO3 and brine. The solvent was dried over sodium sulfate and removed in vacuo. The resulting residue was purified on normal phase chromatography (EtOAc/heptane) to yield tert-butyl 4-(3-bromo-5-methoxyphenoxy)piperidine-1-carboxylate. MH+ 386.2, 388.2 added slowly to the mixture, which washed with saturated NaHCO3 and brine The solvent was dried over sodium sulfate removed in vacuo The resulting residue was purified on normal phase chromatography (EtOAc/heptane)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Bromo-5-methoxyphenol (0.18 g, 0.89 mmol) and triphenylphosphine (0.284, 1.07 mmol) were taken into THF (5 mL) and the resulting mixture cooled to 0° C. 4-Hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.18 g, 0.89 mmol), and DIAD (0.207 mL, 1.07 mmol) were taken up into THF (5 mL) and added slowly to the mixture, which was then stirred at room temperature over night. The resulting mixture was taken into EtOAc and washed with saturated NaHCO3 and brine. The solvent was dried over sodium sulfate and removed in vacuo. The resulting residue was purified on normal phase chromatography (EtOAc/heptane) to yield tert-butyl 4-(3-bromo-5-methoxyphenoxy)piperidine-1-carboxylate. MH+ 386.2, 388.2 added slowly to the mixture, which washed with saturated NaHCO3 and brine The solvent was dried over sodium sulfate removed in vacuo The resulting residue was purified on normal phase chromatography (EtOAc/heptane)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-3,5-dimethoxy-benzene (0.217 g, 0.001 mol) and KCN (0.20 g, 0.003 mol) were taken up into DMSO (10 mL) and the resulting mixture stirred at 120° C. for six hours, then at 150° C. overnight. The mixture was maintained at this temperature, with stirring for another day. The reaction was then quenched with water and the resulting mixture extracted with EtOAc. The organic layer was washed with saturated NaHCO3, brine, then dried over sodium sulfate and the solvent removed in vacuo. The resulting residue was purified on normal phase chromatography (Heptane/EtOAc) to yield 3-bromo-5-methoxyphenol. MH+ 203, 205 at 150° C. overnight The mixture was maintained at this temperature with stirring for another day The reaction was then quenched with water the resulting mixture extracted with EtOAc The organic layer was washed with saturated NaHCO3, brine dried over sodium sulfate the solvent removed in vacuo The resulting residue was purified on normal phase chromatography (Heptane/EtOAc)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-bromo-3,5-dimethyoxybenzene (3.0 g, 13.8 mmol) was dissolved in dichloromethane (45 mL) and the solution was cooled to −78° C. Boron tribromide (1M in dichloromethane, 41 mL, 41 mmol) was added and the solution was warmed gradually to room temperature over 18 hours. After cooling to −78° C., the reaction was quenched with water (100 mL). The organics were separated and washed with sodium thiosulphate solution then water, then dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with pentane:ethyl acetate 100:0 to 80:20, to afford the title compound in 16% yield (470 mg). the solution was warmed gradually to room temperature over 18 hours After cooling to −78° C. the reaction was quenched with water (100 mL) The organics were separated washed with sodium thiosulphate solution water, then dried over magnesium sulfate concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with pentane:ethyl acetate 100:0 to 80:20