methyl 3,4-dihydroxybenzoate

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: To a mixture of methyl 3,4-dihydroxybenzoate (1.0 g, 6.0 mmol), potassium carbonate (3.3 g, 23.8 mmol) and acetonitrile (30 mL) was added 1-bromo-2-(methyloxy)ethane(1.7 mL, 17.9 mmol). The resulting mixture was heated at reflux 18 hour. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (100 mL), filtered and concentrated. The residue was then diluted with ethyl acetate (100 mL) and washed with 5% sodium hydroxide solution, water and brine (100 mL each), dried over sodium sulfate, filtered and concentrated to give an oily residue which was purified by flash chromatography (silica gel, 30%-50% ethyl acetate-hexane) to provide methyl 3,4-bis{[2-(methyloxy)ethyl]oxy}benzoate (1.1 g, 3.9 mmol, 65% yield). 1H NMR (400 MHz, CDCl3): 7.65-7.63 (d, 1H), 7.55 (s, 1H), 6.90-6.88 (d, 1H), 4.21-4.18 (m, 4H), 3.87 (s, 3H), 3.80-3.77 (m, 4H), 3.45 (s, 6H). The resulting mixture was heated at reflux 18 hour filtered concentrated The residue was then diluted with ethyl acetate (100 mL) washed with 5% sodium hydroxide solution, water and brine (100 mL each) dried over sodium sulfate filtered concentrated to give an oily residue which was purified by flash chromatography (silica gel, 30%-50% ethyl acetate-hexane)

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

Procedure: To a mixture of methyl 3,4-dihydroxybenzoate (1.0 g, 6.0 mmol), potassium carbonate (3.3 g, 23.8 mmol) and acetonitrile (30 mL) was added 1-bromo-2-(methyloxy)ethane(1.7 mL, 17.9 mmol). The resulting mixture was heated at reflux 18 hour. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (100 mL), filtered and concentrated. The residue was then diluted with ethyl acetate (100 mL) and washed with 5% sodium hydroxide solution, water and brine (100 mL each), dried over sodium sulfate, filtered and concentrated to give an oily residue which was purified by flash chromatography (silica gel, 30%-50% ethyl acetate-hexane) to provide methyl 3,4-bis{[2-(methyloxy)ethyl]oxy}benzoate (1.1 g, 3.9 mmol, 65% yield). 1H NMR (400 MHz, CDCl3): 7.65-7.63 (d, 1H), 7.55 (s, 1H), 6.90-6.88 (d, 1H), 4.21-4.18 (m, 4H), 3.87 (s, 3H), 3.80-3.77 (m, 4H), 3.45 (s, 6H). The resulting mixture was heated at reflux 18 hour filtered concentrated The residue was then diluted with ethyl acetate (100 mL) washed with 5% sodium hydroxide solution, water and brine (100 mL each) dried over sodium sulfate filtered concentrated to give an oily residue which was purified by flash chromatography (silica gel, 30%-50% ethyl acetate-hexane)

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

Procedure: A mixture of 25 g of product from Example 102, 72.3 g of 1-iodoheptane, 61.65 g of potassium carbonate and 500 ml of 2-butanone is heated at reflux temperature for 44 hours. The cooled reaction mixture is filtered and concentrated in vacuo. The oily residue is purified by chromatography (silica gel: 10% ethyl acetate/hexane) to give 53.7 g of the desired product. is heated at reflux temperature for 44 hours The cooled reaction mixture is filtered concentrated in vacuo The oily residue is purified by chromatography (silica gel: 10% ethyl acetate/hexane)

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

Procedure: A mixture of 25 g of product from Example 102, 72.3 g of 1-iodoheptane, 61.65 g of potassium carbonate and 500 ml of 2-butanone is heated at reflux temperature for 44 hours. The cooled reaction mixture is filtered and concentrated in vacuo. The oily residue is purified by chromatography (silica gel: 10% ethyl acetate/hexane) to give 53.7 g of the desired product. is heated at reflux temperature for 44 hours The cooled reaction mixture is filtered concentrated in vacuo The oily residue is purified by chromatography (silica gel: 10% ethyl acetate/hexane)

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

Procedure: A mixture of 15.0 g of product from Example 102, 53.2 g of 1-bromotetradecane, 37 g of potassium carbonate, 1.04 g of potassium iodide and 350 ml of 2-butanone is heated at reflux for 28.5 hours. The reaction is cooled to room temperature, filtered and the filtrate concentrated in vacuo. The residue is recrystallized from methylene chloride/hexane to give 49.33 g of the desired product. is heated at reflux for 28.5 hours filtered the filtrate concentrated in vacuo The residue is recrystallized from methylene chloride/hexane

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

Procedure: A mixture of 15.0 g of product from Example 102, 53.2 g of 1-bromotetradecane, 37 g of potassium carbonate, 1.04 g of potassium iodide and 350 ml of 2-butanone is heated at reflux for 28.5 hours. The reaction is cooled to room temperature, filtered and the filtrate concentrated in vacuo. The residue is recrystallized from methylene chloride/hexane to give 49.33 g of the desired product. is heated at reflux for 28.5 hours filtered the filtrate concentrated in vacuo The residue is recrystallized from methylene chloride/hexane

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

Procedure: A mixture of 100 g of 3,4-dihydroxy benzoic acid, 600 ml methyl alcohol and 10 ml of concentrated sulfuric acid is heated at reflux for 18 hours. The reaction mixture is cooled to room temperature, poured into water and extracted with methylene chloride. The organic layer is washed with saturated sodium bicarbonate and sodium chloride, dried and concentrated in vacuo to give 50.6 g of the desired product. is heated at reflux for 18 hours extracted with methylene chloride The organic layer is washed with saturated sodium bicarbonate and sodium chloride dried concentrated in vacuo

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

Procedure: A mixture of 100 g of 3,4-dihydroxy benzoic acid, 600 ml methyl alcohol and 10 ml of concentrated sulfuric acid is heated at reflux for 18 hours. The reaction mixture is cooled to room temperature, poured into water and extracted with methylene chloride. The organic layer is washed with saturated sodium bicarbonate and sodium chloride, dried and concentrated in vacuo to give 50.6 g of the desired product. is heated at reflux for 18 hours extracted with methylene chloride The organic layer is washed with saturated sodium bicarbonate and sodium chloride dried concentrated in vacuo

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

Procedure: 120 g of 3,4-dihydroxybenzoic acid methyl ester was subjected to reaction with 340 ml of methanol and 340 ml of hydrazine hydrate over 3 days at room temperature. Then 340 ml of water was added thereto and the solvent was evaporated in vacuum. Addition of water and evaporation were repeated twice. Subsequently the product was crystallized from 340 ml of water. m.p. 260° C. (decomposed). the solvent was evaporated in vacuum Addition of water and evaporation Subsequently the product was crystallized from 340 ml of water

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

Procedure: 120 g of 3,4-dihydroxybenzoic acid methyl ester was subjected to reaction with 340 ml of methanol and 340 ml of hydrazine hydrate over 3 days at room temperature. Then 340 ml of water was added thereto and the solvent was evaporated in vacuum. Addition of water and evaporation were repeated twice. Subsequently the product was crystallized from 340 ml of water. m.p. 260° C. (decomposed). the solvent was evaporated in vacuum Addition of water and evaporation Subsequently the product was crystallized from 340 ml of water