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

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

Procedure: To a solution of methyl (2-hydroxyphenyl)acetate (14 g, 84.3 mmol) in 100 mL of DCM was added diisopropyl-amine (1.7 g, 16.8 mmol) and NBS (15 g, 84.2 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h. The reaction was poured into 1N HCl, extracted with DCM, and concentrated to give crude methyl (3-bromo-2-hydroxyphenyl)acetate. Step C: methyl (3-bromo-2-methoxyphenyl)acetate extracted with DCM concentrated

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:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butylamine (1.74 mL, 16.4 mmol, 1.50 eq.) in toluene (54 mL), bromine (0.47 mL, 9.2 mmol, 0.84 eq.) was added dropwise at −30° C. The mixture was stirred at −30° C. for 1 hour then cooled down to −78° C. and a solution of methyl 2-(2-hydroxyphenyl)acetate (1.82 g, 11.0 mmol, 1.00 eq.) in DCM (10 mL) was slowly added. The resulting mixture was stirred at r.t. for 18 hours. Water was added and the layers were separated. The aq. phase was extracted with DCM (2×). The comb. org. layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by prep. HPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated to give (3-bromo-2-hydroxy-phenyl)-acetic acid methyl ester as a pale yellow oil that solidified upon standing. then cooled down to −78° C. The resulting mixture was stirred at r.t. for 18 hours the layers were separated The aq. phase was extracted with DCM (2×) layers were dried over MgSO4 filtered concentrated in vacuo The residue was purified by prep HPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated

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

Procedure: To a solution of methyl (2-hydroxyphenyl)acetate (14.0 g, 84.3 mmol) in 100 mL of DCM was added diisopropyl-amine (1.70 g, 16.8 mmol) and NBS (15 g, 84.2 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h. The reaction was poured into 1N HCl, extracted with DCM, and concentrated to give crude methyl (3-bromo-2-hydroxyphenyl)acetate. extracted with DCM 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:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl(2-hydroxyphenyl)acetate (14.0 g, 84.3 mmol) in 100 mL of DCM was added diisopropyl-amine (1.70 g, 16.8 mmol) and NBS (15 g, 84.2 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h. The reaction was poured into 1N HCl, extracted with DCM, and concentrated to give crude methyl(3-bromo-2-hydroxyphenyl)acetate. extracted with DCM concentrated