methyl 2-(3,4-dihydroxyphenyl)acetate

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

Procedure: A mixture of 3,4-dihydroxyphenylacetic acid (10.0 g) and concentrated sulphuric acid (0.5 ml ) in methanol (70 ml) was heated under reflux for 16 hours. The mixture was concentrated, water was added and the mixture was neutralised to pH7 using sodium carbonate. The cloudy solution obtained was extracted with dichloromethane (200 ml), dried (Na2SO4) and evaporated to give a yellow gum (7.64 g). LRMS m/z=183(m+1)+. was heated under reflux for 16 hours The mixture was concentrated water was added The cloudy solution obtained was extracted with dichloromethane (200 ml) dried (Na2SO4) evaporated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of di(4-chlorophenyl)dimethoxymethane (26 g) (see Preparation 13) and methyl (3,4-dihydroxyphenyl)acetate (16 g) (see Preparation 12) in toluene (200 ml) was heated under reflux in a Dean-Stark apparatus for one hour. The reaction was cooled to 60° C. and p-toluenesulphonic acid was added (50 mg). After heating under reflux for 16 hours the solution was cooled, washed with aqueous sodium bicarbonate (100 ml, dried (MgSO4) and evaporated to a brown gum. Flash chromatography (silica, eluant=4:1 hexane/ethyl acetate) gave the title compound as a pale yellow gum (13.7 g). LRMS m/z=415(m)+. was heated under reflux in a Dean-Stark apparatus for one hour After heating under reflux for 16 hours the solution was cooled washed with aqueous sodium bicarbonate (100 ml dried (MgSO4) evaporated to a brown gum

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl 2-(3,4-dihydroxyphenyl)acetate (1.0 g) in DMF (10 mL) was added tert-butyl 2-bromoethylcarbamate (2.7 g) and K2CO3 (1.7 g). The resulting reaction mixture was stirred at 60° C. overnight. Water was added and the aqueous phase extracted with EtOAc. The organic phase was then dried and concentrated. The residue was purified by flash chromatography. The product was obtained as a mixture of mono- and bis-alkylation. The mixture was then dissolved in MeOH and THF (10 mL, 1:1) and 1N NaOH was added. The resulting reaction mixture was stirred at room temperature overnight. 1N HCl was added to acidify the solution. The aqueous phase was extracted with EtOAc (3×). The organic phases were combined, dried and concentrated. The title product was obtained by reverse phase chromatography purification (0.5 g). The resulting reaction mixture the aqueous phase extracted with EtOAc The organic phase was then dried concentrated The residue was purified by flash chromatography The product was obtained as a mixture of mono- and bis-alkylation The resulting reaction mixture was stirred at room temperature overnight The aqueous phase was extracted with EtOAc (3×) dried concentrated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl 2-(3,4-dihydroxyphenyl)acetate (1.0 g) in DMF (10 mL) was added tert-butyl 2-bromoethylcarbamate (2.7 g) and K2CO3 (1.7 g). The resulting reaction mixture was stirred at 60° C. overnight. Water was added and the aqueous phase extracted with EtOAc. The organic phase was then dried and concentrated. The residue was purified by flash chromatography. The product was obtained as a mixture of mono- and bis-alkylation. The mixture was then dissolved in MeOH and THF (10 mL, 1:1) and 1N NaOH was added. The resulting reaction mixture was stirred at room temperature overnight. 1N HCl was added to acidify the solution. The aqueous phase was extracted with EtOAc (3×). The organic phases were combined, dried and concentrated. The title product was obtained by reverse phase chromatography purification (0.5 g). The resulting reaction mixture the aqueous phase extracted with EtOAc The organic phase was then dried concentrated The residue was purified by flash chromatography The product was obtained as a mixture of mono- and bis-alkylation The resulting reaction mixture was stirred at room temperature overnight The aqueous phase was extracted with EtOAc (3×) dried concentrated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of di(4-chlorophenyl)dimethoxymethane (26 g) (see Preparation 13) and methyl (3,4-dihydroxyphenyl)acetate (16 g) (see Preparation 12) in toluene (200 ml) was heated under reflux in a Dean-Stark apparatus for one hour. The reaction was cooled to 60° C. and p-toluenesulphonic acid was added (50 mg). After heating under reflux for 16 hours the solution was cooled, washed with aqueous sodium bicarbonate (100 ml), dried (MgSO4) and evaporated to a brown gum. Flash chromatography (silica, eluant=4:1 hexane/ethyl acetate) gave the title compound as a pale yellow gum (13.7 g). LRMS m/z=415(m)+. was heated under reflux in a Dean-Stark apparatus for one hour After heating under reflux for 16 hours the solution was cooled washed with aqueous sodium bicarbonate (100 ml) dried (MgSO4) evaporated to a brown gum

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl 2-(3,4-dihydroxyphenyl)acetate (1.0 g) in DMF (10 mL) was added tert-butyl 2-bromoethylcarbamate (2.7 g) and K2CO3 (1.7 g). The resulting reaction mixture was stirred at 60° C. overnight. Water was added and the aqueous phase extracted with EtOAc. The organic phase was then dried and concentrated. The residue was purified by flash chromatography. The product was obtained as a mixture of mono- and bis-alkylation. The mixture was then dissolved in MeOH and THF (10 mL, 1:1) and IN NaOH was added. The resulting reaction mixture was stirred at room temperature overnight. IN HCl was added to acidify the solution. The aqueous phase was extracted with EtOAc (3×). The organic phases were combined, dried and concentrated. The title product was obtained by reverse phase chromatography purification (0.5 g). The resulting reaction mixture the aqueous phase extracted with EtOAc The organic phase was then dried concentrated The residue was purified by flash chromatography The product was obtained as a mixture of mono- and bis-alkylation The resulting reaction mixture was stirred at room temperature overnight The aqueous phase was extracted with EtOAc (3×) dried concentrated

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

Procedure: 3,4-Dihydroxyphenylacetic acid is refluxed in methanol in the presence of sulfuric acid, to give methyl 2-(3,4-dihydroxyphenyl)acetate.

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

Procedure: A mixture of 3,4-dihydroxyphenylacetic acid (10.0 g) and concentrated sulphuric acid (0.5 ml ) in methanol (70 ml) was heated under reflux for 16 hours. The mixture was concentrated, water was added and the mixture was neutralised to pH7 using sodium carbonate. The cloudy solution obtained was extracted with dichloromethane (200 ml), dried (Na2SO4) and evaporated to give a yellow gum (7.64 g). LRMS m/z=183(m+1)+. was heated under reflux for 16 hours The mixture was concentrated water was added The cloudy solution obtained was extracted with dichloromethane (200 ml) dried (Na2SO4) evaporated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of di(4-chlorophenyl)dimethoxymethane (26 g) (see Preparation 13) and methyl (3,4-dihydroxyphenyl)acetate (16 g) (see Preparation 12) in toluene (200 ml) was heated under reflux in a Dean-Stark apparatus for one hour. The reaction was cooled to 60° C. and p-toluenesulphonic acid was added (50 mg). After heating under reflux for 16 hours the solution was cooled, washed with aqueous sodium bicarbonate (100 ml, dried (MgSO4) and evaporated to a brown gum. Flash chromatography (silica, eluant=4:1 hexane/ethyl acetate) gave the title compound as a pale yellow gum (13.7 g). LRMS m/z=415(m)+. was heated under reflux in a Dean-Stark apparatus for one hour After heating under reflux for 16 hours the solution was cooled washed with aqueous sodium bicarbonate (100 ml dried (MgSO4) evaporated to a brown gum

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl 2-(3,4-dihydroxyphenyl)acetate (1.0 g) in DMF (10 mL) was added tert-butyl 2-bromoethylcarbamate (2.7 g) and K2CO3 (1.7 g). The resulting reaction mixture was stirred at 60° C. overnight. Water was added and the aqueous phase extracted with EtOAc. The organic phase was then dried and concentrated. The residue was purified by flash chromatography. The product was obtained as a mixture of mono- and bis-alkylation. The mixture was then dissolved in MeOH and THF (10 mL, 1:1) and 1N NaOH was added. The resulting reaction mixture was stirred at room temperature overnight. 1N HCl was added to acidify the solution. The aqueous phase was extracted with EtOAc (3×). The organic phases were combined, dried and concentrated. The title product was obtained by reverse phase chromatography purification (0.5 g). The resulting reaction mixture the aqueous phase extracted with EtOAc The organic phase was then dried concentrated The residue was purified by flash chromatography The product was obtained as a mixture of mono- and bis-alkylation The resulting reaction mixture was stirred at room temperature overnight The aqueous phase was extracted with EtOAc (3×) dried concentrated