methyl 2-(3-bromo-2-methoxyphenyl)acetate

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

Procedure: 2-(3-bromo-2-methoxyphenypethanol To a solution of methyl (3-bromo-2-methoxyphenyl)acetate (8.2 g, 31.66 mmol) in 200 mL of dry THF under N2 at room temperature was added LiBH4 (32 mL, 63.32 mmol, 2M THF). After 1.5 hours, the reaction was warmed to reflux for 3 hours, and then cooled to room temperature. The solution was poured into EtOAc/1N HCl solution, and the layers were separated. The organic layer was washed with water, saturated Na2CO3 and brine, dried over anhydrous Na2SO4 and concentrated to give 2-(3-bromo-2-methoxyphenyl)ethanol. Step E: methyl 6-bromo-5-methoxy-3,4-dihydro-1H-isochromene-1-carboxylate TiCl4 (9.84 g, 104 mmol) was added over a period of 20 min to an ice-cooled mixture of 2-(3-bromo-2-methoxyphenyl)ethanol (6 g, 26.0 mmol) and ethyl diethoxyacetate (5.5 g, 31.1 mmol) in 60 mL of CH3NO2. After stirred for 10 min, the ice bath was removed and the mixture was allowed to stir at room temperature over night. The mixture was poured onto ice/aqueous 1N HCl. Extracted by DCM and backwashed with 1N HCl and brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified via column chromatograph to give methyl 6-bromo-5-methoxy-3,4-dihydro-1H-isochromene-1-carboxylate. the reaction was warmed to reflux for 3 hours the layers were separated The organic layer was washed with water, saturated Na2CO3 and brine dried over anhydrous Na2SO4 concentrated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl (3-bromo-2-hydroxyphenyl)acetate (18.7 g, 76.33 mmol) in 200 mL of DMF was added K2CO3 (52.7 g, 381.6 mmol), MeI (14 mL, 228.9 mmol). The mixture was stirred at 50° C. for 3 hours. The reaction solution was diluted with EtOAc and water. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified column chromatography to give methyl (3-bromo-2-methoxyphenyl)acetate. The organic layer was dried over anhydrous sodium sulfate concentrated The residue was purified column chromatography

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (3-bromo-2-hydroxy-phenyl)-acetic acid methyl ester (866 mg, 3.5 mmol, 1 eq.) and potassium carbonate (2.44 g, 17.7 mmol, 5 eq.) in MeCN (9 mL), iodomethane (0.67 mL, 10.6 mmol, 3 eq.) was added. The resulting mixture was stirred at 50° C. for 2 hours. The reaction mixture was diluted with AcOEt and water. The layers were separated and the aq. phase was extracted with AcOEt (2×). The comb. org. layers were dried over MgSO4, filtered, and concentrated in vacuo to give the title compound as an orange oil. The product was used without further purification. The layers were separated the aq. phase was extracted with AcOEt (2×) layers were dried over MgSO4 filtered concentrated in vacuo

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

Procedure: To a solution of methyl [3-bromo-2-(methyloxy)phenyl]acetate (8.20 g, 31.7 mmol) in 200 mL of dry THF under N2 at room temperature was added LiBH4 (32 mL, 63.32 mmol, 2M THF). After 1.5 hours, the reaction was warmed to reflux for 3 hours, and then cooled to room temperature. The solution was poured into EtOAc/1N HCl solution, and the layers were separated. The organic layer was washed with water, saturated Na2CO3 and brine, dried over anhydrous Na2SO4 and concentrated to give 2[3-bromo-2-(methyloxy)phenyl]ethanol the reaction was warmed to reflux for 3 hours the layers were separated The organic layer was washed with water, saturated Na2CO3 and brine dried over anhydrous Na2SO4 concentrated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl (3-bromo-2-hydroxyphenyl)acetate (18.7 g, 76.3 mmol) in 200 mL of DMF was added K2CO3 (52.7 g, 382 mmol), MeI (14.0 mL, 229 mmol). The mixture was stirred at 50° C. for 3 hours. The reaction solution was diluted with EtOAc and water. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified column chromatography to give methyl [3-bromo-2-(methyloxy)phenyl]acetate. The organic layer was dried over anhydrous sodium sulfate concentrated The residue was purified column chromatography

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

Procedure: To a solution of methyl[3-bromo-2-(methyloxy)phenyl]acetate (8.20 g, 31.7 mmol) in 200 mL of dry THF under N2 at room temperature was added LiBH4 (32 mL, 63.32 mmol, 2M THF). After 1.5 hours, the reaction was warmed to reflux for 3 hours, and then cooled to room temperature. The solution was poured into EtOAc/1N HCl solution, and the layers were separated. The organic layer was washed with water, saturated Na2CO3 and brine, dried over anhydrous Na2SO4 and concentrated to give 2-[3-bromo-2-(methyloxy)phenyl]ethanol the reaction was warmed to reflux for 3 hours the layers were separated The organic layer was washed with water, saturated Na2CO3 and brine dried over anhydrous Na2SO4 concentrated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl(3-bromo-2-hydroxyphenyl)acetate (18.7 g, 76.3 mmol) in 200 mL of DMF was added K2CO3 (52.7 g, 382 mmol), MeI (14.0 mL, 229 mmol). The mixture was stirred at 50° C. for 3 hours. The reaction solution was diluted with EtOAc and water. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified column chromatography to give methyl[3-bromo-2-(methyloxy)phenyl]acetate. The organic layer was dried over anhydrous sodium sulfate concentrated The residue was purified column chromatography