3-hydroxy-4-(2-methoxyethoxy)benzaldehyde

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

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

Procedure: An amount of 3-hydroxy-4-(2-methoxyethoxy)benzaldehyde (1.24 g, 6.32 mmol) in 20 mL of EtOH and 10 mL of pyridine is added methoxy]amine hydrochloride (1.06 g, 12.64 mmol). The reaction mixture is stirred at room temperature over weekend. Solvent is removed under vacuum to give colorless oil which is added ether, washed twice with saturated NaHCO3 solution, once with brine, dried over Mg2SO4, filtered and evaporated to give colorless oil. Leaving this oil overnight at room temperature gave 1.15 g (81.0% yield) of colorless solid: mp: 63-64° C.; MS (ESI) m/z 226.1 (M+H)+1 Solvent is removed under vacuum to give colorless oil which washed twice with saturated NaHCO3 solution, once with brine dried over Mg2SO4 filtered evaporated to give colorless oil Leaving this oil overnight at room temperature

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

Procedure: An amount of 3-hydroxy-4-(2-methoxyethoxy)benzaldehyde (1.24 g, 6.32 mmol) in 20 mL of EtOH and 10 mL of pyridine is added methoxy]amine hydrochloride (1.06 g, 12.64 mmol). The reaction mixture is stirred at room temperature over weekend. Solvent is removed under vacuum to give colorless oil which is added ether, washed twice with saturated NaHCO3 solution, once with brine, dried over Mg2SO4, filtered and evaporated to give colorless oil. Leaving this oil overnight at room temperature gave 1.15 g (81.0% yield) of colorless solid: mp: 63-64° C.; MS (ESI) m/z 226.1 (M+H)+1 Solvent is removed under vacuum to give colorless oil which washed twice with saturated NaHCO3 solution, once with brine dried over Mg2SO4 filtered evaporated to give colorless oil Leaving this oil overnight at room temperature

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

Procedure: An amount of 3-hydroxy-4-(2-methoxyethoxy)benzaldehyde (1.24 g, 6.32 mmol) in 20 mL of EtOH and 10 mL of pyridine is added methoxy]amine hydrochloride (1.06 g, 12.64 mmol). The reaction mixture is stirred at room temperature over weekend. Solvent is removed under vacuum to give colorless oil which is added ether, washed twice with saturated NaHCO3 solution, once with brine, dried over Mg2SO4, filtered and evaporated to give colorless oil. Leaving this oil overnight at room temperature gave 1.15 g (81.0% yield) of colorless solid: mp: 63-64° C.; MS (ESI) m/z 226.1 (M+H)+1 Solvent is removed under vacuum to give colorless oil which washed twice with saturated NaHCO3 solution, once with brine dried over Mg2SO4 filtered evaporated to give colorless oil Leaving this oil overnight at room temperature

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

Procedure: An amount of 3,4-dihydroxybenzaldehyde (5.0 g, 36.2 mmol) in 20 mL of N,N′-dimethylformamide is added 2-bromoethyl methyl ether (3.4 mL, 36.2 mmol), and sodium carbonate (5.0 g, 72.4 mmol). The reaction mixture is stirred at room temperature for 3 days. After removal solids by filtration, the solution is subsequently evaporated under high-pressure vacuum to dark brown liquid. The residue is added water and acidified with 12 N HCl solution to pH˜2, then extracted 4×100 mL of EtOAc. The combined organic layer is washed with brine, dried over Mg2SO4, stirred in darko, filtered and evaporated to give yellow liquid. Purification is performed by column chromatography over silica gel using 40% EtOAc/Hex as eluent to give 2.13 g of colorless solid: mp 74-75° C.; MS (ESI) m/z 195.1 (M+H)−1 After removal solids by filtration the solution is subsequently evaporated under high-pressure vacuum to dark brown liquid The residue is added water extracted 4×100 mL of EtOAc The combined organic layer is washed with brine dried over Mg2SO4 stirred in darko filtered evaporated to give yellow liquid Purification

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

Procedure: An amount of 3,4-dihydroxybenzaldehyde (5.0 g, 36.2 mmol) in 20 mL of N,N′-dimethylformamide is added 2-bromoethyl methyl ether (3.4 mL, 36.2 mmol), and sodium carbonate (5.0 g, 72.4 mmol). The reaction mixture is stirred at room temperature for 3 days. After removal solids by filtration, the solution is subsequently evaporated under high-pressure vacuum to dark brown liquid. The residue is added water and acidified with 12 N HCl solution to pH˜2, then extracted 4×100 mL of EtOAc. The combined organic layer is washed with brine, dried over Mg2SO4, stirred in darko, filtered and evaporated to give yellow liquid. Purification is performed by column chromatography over silica gel using 40% EtOAc/Hex as eluent to give 2.13 g of colorless solid: mp 74-75° C.; MS (ESI) m/z 195.1 (M+H)−1 After removal solids by filtration the solution is subsequently evaporated under high-pressure vacuum to dark brown liquid The residue is added water extracted 4×100 mL of EtOAc The combined organic layer is washed with brine dried over Mg2SO4 stirred in darko filtered evaporated to give yellow liquid Purification

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium carbonate (11.8 g, 85.7 mmol) and benzyl chloride (10 mL, 86.9 mmol) were added to a liquid mixture of 3-hydroxy-4-(2-methoxyethoxy)benzaldehyde described in Production Example 20-1 (12.9 g, 65.9 mmol) in ethanol (130 mL) under nitrogen atmosphere at room temperature, and the mixture was heated under reflux at 90° C. for 2 hours. The mixture was cooled to 0° C. and then 2 M hydrochloric acid, ethyl acetate, and water were added for partition. The organic layer was washed with a saturated saline solution, dried over anhydrous magnesium sulfate, and then filtered. The solvent was evaporated and the resultant residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=9:1-1:1). The target fraction was concentrated under vacuum to obtain the title compound (17.6 g, 93%). the mixture was heated The mixture was cooled to 0° C. for partition The organic layer was washed with a saturated saline solution dried over anhydrous magnesium sulfate filtered The solvent was evaporated the resultant residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=9:1-1:1) The target fraction was concentrated under vacuum

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

Procedure: Commercially available 3,4-dihydroxybenzaldehyde (39.3 g, 285 mmol) and sodium carbonate (45.2 g, 427 mmol) were dissolved in N,N-dimethylformamide (400 mL), then commercially available 2-bromoethyl methyl ether (26.7 mL, 285 mmol) was added under nitrogen atmosphere at room temperature, and the mixture was stirred for 5 days. The mixture was cooled to 0° C. and then 2 M hydrochloric acid, ethyl acetate, and water were added for partition. The aqueous layer was extracted with ethyl acetate, then the combined organic layer was washed with a saturated saline solution and dried over anhydrous magnesium sulfate, and then filtered. The solvent was evaporated, dichloromethane was added, the precipitate was separated by filtration, and then the resultant filtrate was purified with silica gel column chromatography (n-heptane:ethyl acetate=17:3-1:1). The target fraction was concentrated under vacuum to obtain the title compound (12.9 g, 23%). for partition The aqueous layer was extracted with ethyl acetate the combined organic layer was washed with a saturated saline solution dried over anhydrous magnesium sulfate filtered The solvent was evaporated dichloromethane was added the precipitate was separated by filtration the resultant filtrate was purified with silica gel column chromatography (n-heptane:ethyl acetate=17:3-1:1) The target fraction was concentrated under vacuum