methyl 4-(bromomethyl)-2-hydroxybenzoate

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

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

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

Procedure: Methyl 4-methylsalicylate (98.1 g, 590 mmoles) was dissolved in carbon tetrachloride (600 mL), and N-bromosuccinimide (105.0 g, 590 mmoles) and benzoyl peroxide (0.7 g 3 mmoles) were added. The mixture was refluxed under nitrogen. After 2 hours, an additional portion (0.7 g) of N-bromosuccinimide was added. Reflux was continued for 16 hours. The reaction mixture was cooled to room temperature and the solid removed by filtration. The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified on standing. Hexanes (500 mL) was added to the solid, and the mixture was boiled until almost all solids dissolved. The hot hexanes solution was filtered and concentrated until a solid just began to precipitate. The mixture was heated to dissolve the solid, and the solution was allowed to cool slowly to room temperature. Pale yellow crystals formed slowly. The mixture was then chilled in ice for 2 hours to complete crystallization. Finally, the solid was filtered, washed with cold hexanes (100 mL), and dried in vacuo to afford 83.5 g (58% yield) of methyl 4-bromomethylsalicylate (m.p. 73°-75° C., open capillary, uncorrected). The mixture was refluxed under nitrogen Reflux was continued for 16 hours the solid removed by filtration The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified dissolved The hot hexanes solution was filtered concentrated until a solid to precipitate The mixture was heated to dissolve the solid to cool slowly to room temperature Pale yellow crystals formed slowly The mixture was then chilled in ice for 2 hours crystallization Finally, the solid was filtered washed with cold hexanes (100 mL) dried in vacuo

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

Procedure: Methyl 4-methylsalicylate (98.1 g, 590 mmoles) was dissolved in carbon tetrachloride (600 mL), and N-bromosuccinimide (105.0 I, 590 mmoles) and benzoyl peroxide (0.7 g, 3 mmoles) were added. The mixture was refluxed under nitrogen. After 2 hours, an additional portion (0.7 g) of N-bromosuccinimide was added. Reflux was continued for 16 hours. The reaction mixture was cooled to room temperature and the solid removed by filtration: The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified on standing. Hexanes (500 mL) was added to the solid, and the mixture was boiled until almost all solids dissolved. The hot hexanes solution was filtered and concentrated until a solid just began to precipitate. The mixture was heated to dissolve the solid, and the solution was allowed to cool slowly to room temperature. Pale yellow crystals formed slowly. The mixture was then chilled in ice for 2 hours to complete crystallization. Finally, the solid was filtered, washed with cold hexanes (100 mL), and dried in vacuo to afford 83.5 g (58% yield) of methyl 4bromomethylsalicylate (m.p. 73°-750 C., open capillary, uncorrected). The mixture was refluxed under nitrogen Reflux was continued for 16 hours the solid removed by filtration The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified dissolved The hot hexanes solution was filtered concentrated until a solid to precipitate The mixture was heated to dissolve the solid to cool slowly to room temperature Pale yellow crystals formed slowly The mixture was then chilled in ice for 2 hours crystallization Finally, the solid was filtered washed with cold hexanes (100 mL) dried in vacuo

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

Procedure: Methyl 4-methylsalicylate (98.1 g, 590 mmoles) was dissolved in carbon tetrachloride (600 mL), and N-bromosuccinimide (105.0 g, 590 mmoles) and benzoyl peroxide (0.7 g, 3 mmoles) were added. The mixture was refluxed under nitrogen. After 2 hours, an additional portion (0.7 g) of N-bromosuccinimide was added. Reflux was continued for 16 hours. The reaction mixture was cooled to room temperature and the solid removed by filtration. The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified on standing. Hexanes (500 mL) was added to the solid, and the mixture was boiled until almost all solids dissolved. The hot hexanes solution was filtered and concentrated until a solid just began to precipitate. The mixture was heated to dissolve the solid, and the solution was allowed to cool slowly to room temperature. Pale yellow crystals formed slowly. The mixture was then chilled in ice for 2 hours to complete crystallization. Finally, the solid was filtered, washed with cold hexanes (100 mL), and dried in vacuo to afford 83.5 g (58% yield) of methyl 4-bromomethylsalicylate (m.p. 73°-75° C., open capillary, uncorrected). The mixture was refluxed under nitrogen Reflux was continued for 16 hours the solid removed by filtration The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified dissolved The hot hexanes solution was filtered concentrated until a solid to precipitate The mixture was heated to dissolve the solid to cool slowly to room temperature Pale yellow crystals formed slowly The mixture was then chilled in ice for 2 hours crystallization Finally, the solid was filtered washed with cold hexanes (100 mL) dried in vacuo

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

Procedure: A refluxing solution of 4-methylsalicylic acid methyl ester (5.1 g, 31.3 mmol) in carbon tetrachloride (50 mL) was treated dropwise with a solution of bromine (1.6 mL, 31.3 mmol) in carbon tetrachloride (5 mL) while under illumination by a 200 W incandescent light bulb. The reaction mixture was stirred for an additional 30 min at reflux and concentrated in vacuo. The residue was dissolved in EtOAc (50 mL) and washed with aqueous sodium thiosulfate (5%, 50 mL), water (50 mL), and brine (50 mL). The organic layer was dried over Na2SO4, concentrated, and the product 4-bromomethylsalicylic acid methyl ester was isolated by recrystallization from heptane (1.6 g, 21%). at reflux concentrated in vacuo The residue was dissolved in EtOAc (50 mL) washed with aqueous sodium thiosulfate (5%, 50 mL), water (50 mL), and brine (50 mL) The organic layer was dried over Na2SO4 concentrated

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

Procedure: Methyl 4-methylsalicylate (98.1 g, 590 mmoles) was dissolved in carbon tetrachloride (600 mL), and N-bromosuccinimide (105.0 g, 590 mmoles) and benzoyl peroxide (0.7 g, 3 mmoles) were added. The mixture was refluxed under nitrogen. After 2 hours, an additional portion (0.7 g) of N-bromosuccinimide was added. Reflux was continued for 16 hours. The reaction mixture was cooled to room temperature and the solid removed by filtration. The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified on standing. Hexanes (500 mL) was added to the solid, and the mixture was boiled until almost all solids dissolved. The hot hexanes solution was filtered and concentrated until a solid just began to precipitate. The mixture was heated to dissolve the solid, and the solution was allowed to cool slowly to room temperature. Pale yellow crystals formed slowly. The mixture was then chilled in ice for 2 hours to complete crystallization. Finally, the solid was filtered, washed with cold hexanes (100 mL), and dried in vacuo to afford 83.5 g (58% yield) of methyl 4-bromomethylsalicylate (m.p. 73°-75° C., open capillary, uncorrected). The mixture was refluxed under nitrogen Reflux was continued for 16 hours the solid removed by filtration The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified dissolved The hot hexanes solution was filtered concentrated until a solid to precipitate The mixture was heated to dissolve the solid to cool slowly to room temperature Pale yellow crystals formed slowly The mixture was then chilled in ice for 2 hours crystallization Finally, the solid was filtered washed with cold hexanes (100 mL) dried in vacuo

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

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

Procedure: Dissolved methyl 4-aminomethyl-2-hydroxybenzoate hydrochloride (13.07 g, 60.1 mmole) and diisopropylethylamine (28.0 mL, 292 mmole) in 225 mL of N,N-dimethyl-formamide by heating slightly until a solution was obtained. Allowed the solution to cool to room temperature and added methyl 4-bromomethyl-2-hydroxybenzoate (9.81 g, 40.0 mmole). The reaction was stirred for 1 day at room temperature. The solution was diluted with 200 mL of 1N HCl and 250 mL of ethyl acetate and allowed to cool to room temperature. Precipitate was collected by filtration, washed with ethyl acetate and dried in vacuo under a under high vacuum. Obtained 11.32 grams (74% yield) of product as a white solid. by heating slightly until a solution was obtained to cool to room temperature Precipitate was collected by filtration washed with ethyl acetate dried in vacuo under a under high vacuum

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

Procedure: Dissolved methyl 4-aminomethyl-2-hydroxybenzoate hydrochloride (13.07 g, 60.1 mmole) and diisopropylethylamine (28.0 mL, 292 mmole) in 225 mL of N,N-dimethyl-formamide by heating slightly until a solution was obtained. Allowed the solution to cool to room temperature and added methyl 4-bromomethyl-2-hydroxybenzoate (9.81 g, 40.0 mmole). The reaction was stirred for 1 day at room temperature. The solution was diluted with 200 mL of 1N HCl and 250 mL of ethyl acetate and allowed to cool to room temperature. Precipitate was collected by filtration, washed with ethyl acetate and dried in vacuo under a under high vacuum. Obtained 11.32 grams (74% yield) of product as a white solid. by heating slightly until a solution was obtained to cool to room temperature Precipitate was collected by filtration washed with ethyl acetate dried in vacuo under a under high vacuum

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

Procedure: Methyl 4-methyl-2-hydroxybenzoate (98.1 g, 590 mmoles) was dissolved in carbon tetrachloride (600 mL), and N-bromosuccinimide (105.0 g, 590 mmoles) and benzoyl peroxide (0.7 g, 3 mmoles) were added. The mixture was refluxed under nitrogen. After 2 hours, an additional portion (0.7 g) of N-bromosuccinimide was added. Reflux was continued for 16 hours. The reaction mixture was cooled to room temperature and the solid removed by filtration. The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified on standing. Hexanes (500 mL) was added to the solid, and the mixture was boiled until almost all solids dissolved. The hot hexanes solution was filtered and concentrated until a solid just began to precipitate. The mixture was heated to dissolve the solid, and the solution was allowed to cool slowly to room temperature. Pale yellow crystals formed slowly. The mixture was then chilled in ice for 2 hours to complete crystallization. Finally, the solid was filtered, washed with cold hexanes (100 mL), and dried in vacuo to afford 83.5 g (58% yield) of methyl 4-bromomethyl-2-hydroxybenzoate (m.p. 73-75° C., open capillary, uncorrected). The mixture was refluxed under nitrogen Reflux was continued for 16 hours the solid removed by filtration The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified dissolved The hot hexanes solution was filtered concentrated until a solid to precipitate The mixture was heated to dissolve the solid to cool slowly to room temperature Pale yellow crystals formed slowly The mixture was then chilled in ice for 2 hours crystallization Finally, the solid was filtered washed with cold hexanes (100 mL) dried in vacuo

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

Procedure: Methyl 4-methyl-2-hydroxybenzoate (98.1 g, 590 mmoles) was dissolved in carbon tetrachloride (600 mL), and N-bromosuccinimide (105.0 g, 590 mmoles) and benzoyl peroxide (0.7 g, 3 mmoles) were added. The mixture was refluxed under nitrogen. After 2 hours, an additional portion (0.7 g) of N-bromosuccinimide was added. Reflux was continued for 16 hours. The reaction mixture was cooled to room temperature and the solid removed by filtration. The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified on standing. Hexanes (500 mL) was added to the solid, and the mixture was boiled until almost all solids dissolved. The hot hexanes solution was filtered and concentrated until a solid just began to precipitate. The mixture was heated to dissolve the solid, and the solution was allowed to cool slowly to room temperature. Pale yellow crystals formed slowly. The mixture was then chilled in ice for 2 hours to complete crystallization. Finally, the solid was filtered, washed with cold hexanes (100 mL), and dried in vacuo to afford 83.5 g (58% yield) of methyl 4-bromomethyl-2-hydroxybenzoate (m.p. 73-75° C., open capillary, uncorrected). The mixture was refluxed under nitrogen Reflux was continued for 16 hours the solid removed by filtration The yellow filtrate was evaporated to dryness to afford a thick yellow syrup that solidified dissolved The hot hexanes solution was filtered concentrated until a solid to precipitate The mixture was heated to dissolve the solid to cool slowly to room temperature Pale yellow crystals formed slowly The mixture was then chilled in ice for 2 hours crystallization Finally, the solid was filtered washed with cold hexanes (100 mL) dried in vacuo