4-bromo-2-(hydroxymethyl)-6-methoxyphenol

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

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

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

Procedure: Sodium borohydride (0.28 g, 6.9 mmol) was added to a THF solution (30 ml) of 5-bromo-2-hydroxy-3-methoxybenzaldehyde (3.2 g 13.8 mmol) under ice cooling and the mixture was stirred at 0° C. for 2 hours. Acetic acid was added to the reaction solution to set pH at 3. 10% hydrochloric acid was added to the reaction mixture, which was then extracted with ethyl acetate. The extracted material was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1→1:1) and concentrated to dryness under reduced pressure to obtain 4-bromo-2-hydroxymethyl-6-methoxyphenol (3.23 g) as light yellow oil. was then extracted with ethyl acetate The extracted material was dried over magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1→1:1) concentrated to dryness under reduced pressure

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

Procedure: Sodium borohydride (0.28 g, 6.9 mmol) was added to a THF solution (30 ml) of 5-bromo-2-hydroxy-3-methoxybenzaldehyde (3.2 g 13.8 mmol) under ice cooling and the mixture was stirred at 0° C. for 2 hours. Acetic acid was added to the reaction solution to set pH at 3. 10% hydrochloric acid was added to the reaction mixture, which was then extracted with ethyl acetate. The extracted material was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1→1:1) and concentrated to dryness under reduced pressure to obtain 4-bromo-2-hydroxymethyl-6-methoxyphenol (3.23 g) as light yellow oil. was then extracted with ethyl acetate The extracted material was dried over magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1→1:1) concentrated to dryness under reduced pressure

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

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

Procedure: To a solution of the 50g of 4-bromo-2-hydroxymethyl-6-methoxyphenol in 450 ml of DMF there was added 20g of sodium hydride (60% oily suspension) while cooling on ice, and the mixture was stirred at room temperature for 30 minutes. After adding 15 ml of bromochloromethane and 3.2 g of sodium iodide to the reaction mixture, it was stirred at 80° C. for 6 hours under a nitrogen atmosphere. Saturated aqueous ammonium chloride was added to the reaction mixture, and extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-heptane) to give the title compound (31.2 g) as a white solid. while cooling on ice was stirred at 80° C. for 6 hours under a nitrogen atmosphere The organic layer was dried over anhydrous magnesium sulfate The desiccating agent was filtered off the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate-heptane)

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

Procedure: Sodium borohydride (0.28 g, 6.9 mmol) was added to a THF solution (30 ml) of 5-bromo-2-hydroxy-3-methoxybenzaldehyde (3.2 g 13.8 mmol) under ice cooling and the mixture was stirred at 0° C. for 2 hours. Acetic acid was added to the reaction solution to set pH at 3. 10% hydrochloric acid was added to the reaction mixture, which was then extracted with ethyl acetate. The extracted material was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1→1:1) and concentrated to dryness under reduced pressure to obtain 4-bromo-2-hydroxymethyl-6-methoxyphenol (3.23 g) as light yellow oil. was then extracted with ethyl acetate The extracted material was dried over magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1→1:1) concentrated to dryness under reduced pressure

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

Procedure: To a solution of the 50 g of 4-bromo-2-hydroxymethyl-6-methoxyphenol in 450 ml of DMF there was added 20 g of sodium hydride (60% oily suspension) while cooling on ice, and the mixture was stirred at room temperature for 30 minutes. After adding 15 ml of bromochloromethane and 3.2 g of sodium iodide to the reaction mixture, it was stirred at 80° C. for 6 hours under a nitrogen atmosphere. Saturated aqueous ammonium chloride was added to the reaction mixture, and extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-heptane) to give the title compound (31.2 g) as a white solid. while cooling on ice was stirred at 80° C. for 6 hours under a nitrogen atmosphere The organic layer was dried over anhydrous magnesium sulfate The desiccating agent was filtered off the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate-heptane)

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

Procedure: To a solution of 50 g of 5-bromo-2-hydroxy-3-methoxybenzaldehyde in 200 ml of an ethanol:THF=1:1 mixed solvent there was added 16.4 g of sodium borohydride while cooling on ice. After stirring at room temperature for 2 hours, 1N hydrochloric acid was added to the reaction mixture while cooling on ice. The organic layer was washed with ethyl acetate and dried over anhydrous magnesium sulfate. The desiccating agent was filtered off, and the filtrate was concentrated under reduced pressure to give the title compound (50 g) as a crude product. while cooling on ice while cooling on ice The organic layer was washed with ethyl acetate dried over anhydrous magnesium sulfate The desiccating agent was filtered off the filtrate was concentrated under reduced pressure

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

Procedure: To a solution of the 50 g of 4-bromo-2-hydroxymethyl-6-methoxyphenol in 450 ml of DMF there was added 20 g of sodium hydride (60% oily suspension) while cooling on ice, and the mixture was stirred at room temperature for 30 minutes. After adding 15 ml of bromochloromethane and 3.2 g of sodium iodide to the reaction mixture, it was stirred at 80° C. for 6 hours under a nitrogen atmosphere. Saturated aqueous ammonium chloride was added to the reaction mixture, and extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-heptane) to give the title compound (31.2 g) as a white solid. while cooling on ice was stirred at 80° C. for 6 hours under a nitrogen atmosphere The organic layer was dried over anhydrous magnesium sulfate The desiccating agent was filtered off the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate-heptane)

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

Procedure: To a solution of 50 g of 5-bromo-2-hydroxy-3-methoxybenzaldehyde in 200 ml of an ethanol:THF=1:1 mixed solvent there was added 16.4 g of sodium borohydride while cooling on ice. After stirring at room temperature for 2 hours, 1N hydrochloric acid was added to the reaction mixture while cooling on ice. The organic layer was washed with ethyl acetate and dried over anhydrous magnesium sulfate. The desiccating agent was filtered off, and the filtrate was concentrated under reduced pressure to give the title compound (50 g) as a crude product. while cooling on ice while cooling on ice The organic layer was washed with ethyl acetate dried over anhydrous magnesium sulfate The desiccating agent was filtered off the filtrate was concentrated under reduced pressure

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

Procedure: To a 450 ml solution of 50 g of 4-bromo-2-hydroxymethyl-6-methoxyphenol in DMF there was added 20 g of sodium hydride (60% mineral oil suspension) while cooling on ice, and the mixture was stirred at room temperature for 30 minutes. After then adding 15 ml of bromochloromethane and 3.2 g of sodium iodide to the reaction mixture, it was stirred at 80° C. for 6 hours under a nitrogen atmosphere. A saturated ammonium chloride aqueous solution was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The desiccant was filtered out and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-heptane system) to obtain the target compound (31.2 g) as a colorless solid. while cooling on ice was stirred at 80° C. for 6 hours under a nitrogen atmosphere The organic layer was dried over anhydrous magnesium sulfate The desiccant was filtered out the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate-heptane system)