methyl 2-(2-bromophenyl)acetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 1.35 g (5.89 mmol) of methyl (2-bromophenyl)acetate are introduced together with 1 g (6.55 mmol) of 6-methoxypyridin-3-ylboronic acid and 1.98 g (13.09 mmol) of caesium fluoride into 20 ml of 1,2-dimethoxyethane under argon. After addition of 0.22 g (0.19 mmol) of tetrakis(triphenylphosphine)palladium(0), the reaction mixture is stirred at 100° C. for 4 h. Cooling to room temperature is followed by addition of a mixture of ethyl acetate and water and extraction with ethyl acetate. After the organic phase has been dried over magnesium sulphate and the solvent has been removed in vacuo, the residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 9:1). 1.1 g (68% of theory) of the product are obtained. Cooling to room temperature After the organic phase has been dried over magnesium sulphate the solvent has been removed in vacuo the residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 9:1) 1.1 g (68% of theory) of the product are obtained

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

Procedure: Hydrochloric acid (gas) was bubbled through 15.8 g (73.5 mmol) 2-bromophenylacetic acid in 100 mL of methanol for 10 min. The resulting solution was partitioned between 100 mL water and 100 mL CH2Cl. The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure to give 16.8 g (73.5 mmol) of methyl-2-bromophenylacetate which was combined with 9.0 g (80.8 mmol) of 1-vinyl-2-pyrrolidinone, and 100 mL of dry THF under argon in a 250 mL round-bottomed flask. The resulting solution was partitioned between 100 mL water and 100 mL CH2Cl The organic layer was dried over MgSO4 the solvent was removed under reduced pressure

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

Procedure: To a solution of 0.484 g (2.91 mmol) of the product of Step F dissolved in 12 mL of acetone were added 0.667 g (2.91 mmol) of methyl 2-bromophenylacetate, 0.804 g (5.82 mmol) of anhydrous K2CO3 and the mixture was stirred and heated at reflux for 5 hours. The mixture was then cooled, filtered and evaporated in vacuo. The residual oil was purified on a silica gel flash chromatography column eluted with 30% ethyl acetate/hexane to afford 0.756 g (83%) of the title compound. heated at reflux for 5 hours The mixture was then cooled filtered evaporated in vacuo The residual oil was purified on a silica gel flash chromatography column eluted with 30% ethyl acetate/hexane

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

Procedure: To a solution of 0.484 g (2.91 mmol) of the product of Step F dissolved in 12 mL of acetone were added 0.667 g (2.91 mmol) of methyl 2-bromophenylacetate, 0.804 g (5.82 mmol) of anhydrous K2CO3 and the mixture was stirred and heated at reflux for 5 hours. The mixture was then cooled, filtered and evaporated in vacuo. The residual oil was purified on a silica gel flash chromatography column eluted with 30% ethyl acetate/hexane to afford 0.756 g (83%) of the title compound. heated at reflux for 5 hours The mixture was then cooled filtered evaporated in vacuo The residual oil was purified on a silica gel flash chromatography column eluted with 30% ethyl acetate/hexane

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

Procedure: To a solution of 0.500 g (2.65 mmol) of 3-chloro-4-hydroxy-5-methoxybenzyl alcohol (Bader) and 0.668 g (1.1 eq) of methyl 2-bromophenylacetate dissolved in 5 mL acetone was added 0.733 g (2 eq) of anhydrous potassium carbonate and the reaction mixture was stirred and refluxed overnight. The reaction mixture was cooled to room temperature, filtered and evaporated in vacuo. The residual oil was purified on a silica gel flash chromatography column eluted with 35% ethyl acetate/hexane to afford 0.570 g (64%) of the title compound. refluxed overnight filtered evaporated in vacuo The residual oil was purified on a silica gel flash chromatography column eluted with 35% ethyl acetate/hexane

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

Procedure: To a solution of 0.500 g (2.65 mmol) of 3-chloro-4-hydroxy-5-methoxybenzyl alcohol (Bader) and 0.668 g (1.1 eq) of methyl 2-bromophenylacetate dissolved in 5 mL acetone was added 0.733 g (2 eq) of anhydrous potassium carbonate and the reaction mixture was stirred and refluxed overnight. The reaction mixture was cooled to room temperature, filtered and evaporated in vacuo. The residual oil was purified on a silica gel flash chromatography column eluted with 35% ethyl acetate/hexane to afford 0.570 g (64%) of the title compound. refluxed overnight filtered evaporated in vacuo The residual oil was purified on a silica gel flash chromatography column eluted with 35% ethyl acetate/hexane

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

Procedure: To a suspension of 0.282 g (7.04 mmol) of a 60% oil dispersion of sodium hydride in DMF was added 1.00 g (7.04 mmol) of 2-chloro-4-methylphenol and the mixture was stirred under an N2 atmosphere at room temperature. After 10 minutes, a solution of 1.94 g (8.45 mmol) of methyl 2-bromophenylacetate dissolved in 10 mL of DMF was added and the reaction was stirred an additional 1.5 hours. The reaction was then diluted into ethyl acetate, washed with water, dried (MgSO4), filtered and evaporated. The residue was purified on a silica gel flash chromatography column eluted with 4% ethyl acetate/hexane to afford 1.70 g (83%) of the title compound. was added the reaction was stirred an additional 1.5 hours washed with water dried (MgSO4) filtered evaporated The residue was purified on a silica gel flash chromatography column eluted with 4% ethyl acetate/hexane