[4-(methoxymethoxy)phenyl]methanol

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

Procedure: Diethyl azodicarboxylate (40% toluene solution, 142 g) was added dropwise to a solution of 4-methoxymethoxybenzylalcohol (50.0 g), N-hydroxyphthalimide (44.1 g) and triphenylphosphine (83.7 g) in tetrahydrofuran (900 ml) at room temperature and stirred for 1 hour. The reaction mixture was concentrated. In order to remove triphenylphosphine oxide, the residue was subjected to silica gel chromatography to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction. The crystals were washed with ethyl acetate-hexane (1:5, v/v) and then dissolved in tetrahydrofuran (200 ml) and ethanol (50 ml). To this solution was added hydrazine monohydrate (33.7 ml) and heated under reflux for 3 hours. The reaction mixture was cooled to room temperature, an aqueous solution of potassium carbonate was added and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. Isopropyl ether was added to the residue and filtered to remove insolubles. The filtrate was concentrated to obtain 4-methoxymethoxybenzyloxyamine (28.9 g, yield 58%) as a colorless oil. The reaction mixture was concentrated In order to remove triphenylphosphine oxide to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction The crystals were washed with ethyl acetate-hexane (1:5 v/v) and then dissolved in tetrahydrofuran (200 ml) To this solution was added hydrazine monohydrate (33.7 ml) heated under reflux for 3 hours an aqueous solution of potassium carbonate was added extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated Isopropyl ether was added to the residue filtered to remove insolubles The filtrate was concentrated

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

Procedure: Chloromethyl methyl ether (34.2 ml) was added to a mixture of 4-hydroxybenzaldehyde (50.0 g), potassium carbonate (84.9 g) and N,N-dimethylformaldehyde (150 ml) at 0° C. and stirred at room temperature for 11 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was dissolved in tetrahydrofuran (300 ml) and methanol (50 ml) and sodium borohydride (7.76 g) was added in portions at 0° C. After stirring for 30 minutes, water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was subjected to silica gel chromatography to obtain 4-methoxymethoxybenzylalcohol (56.7 g, yield 82%) as a colorless oil from an ethyl acetate-hexane (2:3, v/v) eluted fraction. extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated The residue was dissolved in tetrahydrofuran (300 ml) methanol (50 ml) and sodium borohydride (7.76 g) was added in portions at 0° C After stirring for 30 minutes water was added to the reaction mixture extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated

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

Procedure: Chloromethyl methyl ether (34.2 ml) was added to a mixture of 4-hydroxybenzaldehyde (50.0 g), potassium carbonate (84.9 g) and N,N-dimethylformaldehyde (150 ml) at 0° C. and stirred at room temperature for 11 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was dissolved in tetrahydrofuran (300 ml) and methanol (50 ml) and sodium borohydride (7.76 g) was added in portions at 0° C. After stirring for 30 minutes, water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was subjected to silica gel chromatography to obtain 4-methoxymethoxybenzylalcohol (56.7 g, yield 82%) as a colorless oil from an ethyl acetate-hexane (2:3, v/v) eluted fraction. extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated The residue was dissolved in tetrahydrofuran (300 ml) methanol (50 ml) and sodium borohydride (7.76 g) was added in portions at 0° C After stirring for 30 minutes water was added to the reaction mixture extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated

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

Procedure: Diethyl azodicarboxylate (40% toluene solution, 142 g) was added dropwise to a solution of 4-methoxymethoxybenzylalcohol (50.0 g), N-hydroxyphthalimide (44.1 g) and triphenylphosphine (83.7 g) in tetrahydrofuran (900 ml) at room temperature and stirred for 1 hour. The reaction mixture was concentrated. In order to remove triphenylphosphine oxide, the residue was subjected to silica gel chromatography to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction. The crystals were washed with ethyl acetate-hexane (1:5, v/v) and then dissolved in tetrahydrofuran (200 ml) and ethanol (50 ml). To this solution was added hydrazine monohydrate (33.7 ml) and heated under reflux for 3 hours. The reaction mixture was cooled to room temperature, an aqueous solution of potassium carbonate was added and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. Isopropyl ether was added to the residue and filtered to remove insolubles. The filtrate was concentrated to obtain 4-methoxymethoxybenzyloxyamine (28.9 g, yield 58%) as a colorless oil. The reaction mixture was concentrated In order to remove triphenylphosphine oxide to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction The crystals were washed with ethyl acetate-hexane (1:5 v/v) and then dissolved in tetrahydrofuran (200 ml) To this solution was added hydrazine monohydrate (33.7 ml) heated under reflux for 3 hours an aqueous solution of potassium carbonate was added extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated Isopropyl ether was added to the residue filtered to remove insolubles The filtrate was concentrated

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

Procedure: Diethyl azodicarboxylate (40% toluene solution, 142 g) was added dropwise to a solution of 4-methoxymethoxybenzylalcohol (50.0 g), N-hydroxyphthalimide (44.1 g) and triphenylphosphine (83.7 g) in tetrahydrofuran (900 ml) at room temperature and stirred for 1 hour. The reaction mixture was concentrated. In order to remove triphenylphosphine oxide, the residue was subjected to silica gel chromatography to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction. The crystals were washed with ethyl acetate-hexane (1:5, v/v) and then dissolved in tetrahydrofuran (200 ml) and ethanol (50 ml). To this solution was added hydrazine monohydrate (33.7 ml) and heated under reflux for 3 hours. The reaction mixture was cooled to room temperature, an aqueous solution of potassium carbonate was added and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. Isopropyl ether was added to the residue and filtered to remove insolubles. The filtrate was concentrated to obtain 4-methoxymethoxybenzyloxyamine (28.9 g, yield 58%) as a colorless oil. The reaction mixture was concentrated In order to remove triphenylphosphine oxide to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction The crystals were washed with ethyl acetate-hexane (1:5 v/v) and then dissolved in tetrahydrofuran (200 ml) To this solution was added hydrazine monohydrate (33.7 ml) heated under reflux for 3 hours an aqueous solution of potassium carbonate was added extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated Isopropyl ether was added to the residue filtered to remove insolubles The filtrate was concentrated

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

Procedure: Chloromethyl methyl ether (34.2 ml) was added to a mixture of 4-hydroxybenzaldehyde (50.0 g), potassium carbonate (84.9 g) and N,N-dimethylformaldehyde (150 ml) at 0° C. and stirred at room temperature for 11 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was dissolved in tetrahydrofuran (300 ml) and methanol (50 ml) and sodium borohydride (7.76 g) was added in portions at 0° C. After stirring for 30 minutes, water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was subjected to silica gel chromatography to obtain 4-methoxymethoxybenzylalcohol (56.7 g, yield 82%) as a colorless oil from an ethyl acetate-hexane (2:3, v/v) eluted fraction. extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated The residue was dissolved in tetrahydrofuran (300 ml) methanol (50 ml) and sodium borohydride (7.76 g) was added in portions at 0° C After stirring for 30 minutes water was added to the reaction mixture extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated

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

Procedure: Chloromethyl methyl ether (34.2 ml) was added to a mixture of 4-hydroxybenzaldehyde (50.0 g), potassium carbonate (84.9 g) and N,N-dimethylformaldehyde (150 ml) at 0° C. and stirred at room temperature for 11 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was dissolved in tetrahydrofuran (300 ml) and methanol (50 ml) and sodium borohydride (7.76 g) was added in portions at 0° C. After stirring for 30 minutes, water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was subjected to silica gel chromatography to obtain 4-methoxymethoxybenzylalcohol (56.7 g, yield 82%) as a colorless oil from an ethyl acetate-hexane (2:3, v/v) eluted fraction. extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated The residue was dissolved in tetrahydrofuran (300 ml) methanol (50 ml) and sodium borohydride (7.76 g) was added in portions at 0° C After stirring for 30 minutes water was added to the reaction mixture extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated

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

Procedure: Diethyl azodicarboxylate (40% toluene solution, 142 g) was added dropwise to a solution of 4-methoxymethoxybenzylalcohol (50.0 g), N-hydroxyphthalimide (44.1 g) and triphenylphosphine (83.7 g) in tetrahydrofuran (900 ml) at room temperature and stirred for 1 hour. The reaction mixture was concentrated. In order to remove triphenylphosphine oxide, the residue was subjected to silica gel chromatography to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction. The crystals were washed with ethyl acetate-hexane (1:5, v/v) and then dissolved in tetrahydrofuran (200 ml) and ethanol (50 ml). To this solution was added hydrazine monohydrate (33.7 ml) and heated under reflux for 3 hours. The reaction mixture was cooled to room temperature, an aqueous solution of potassium carbonate was added and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. Isopropyl ether was added to the residue and filtered to remove insolubles. The filtrate was concentrated to obtain 4-methoxymethoxybenzyloxyamine (28.9 g, yield 58%) as a colorless oil. The reaction mixture was concentrated In order to remove triphenylphosphine oxide to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction The crystals were washed with ethyl acetate-hexane (1:5 v/v) and then dissolved in tetrahydrofuran (200 ml) To this solution was added hydrazine monohydrate (33.7 ml) heated under reflux for 3 hours an aqueous solution of potassium carbonate was added extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated Isopropyl ether was added to the residue filtered to remove insolubles The filtrate was concentrated

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

Procedure: Diethyl azodicarboxylate (40% toluene solution, 142 g) was added dropwise to a solution of 4-methoxymethoxybenzylalcohol (50.0 g), N-hydroxyphthalimide (44.1 g) and triphenylphosphine (83.7 g) in tetrahydrofuran (900 ml) at room temperature and stirred for 1 hour. The reaction mixture was concentrated. In order to remove triphenylphosphine oxide, the residue was subjected to silica gel chromatography to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction. The crystals were washed with ethyl acetate-hexane (1:5, v/v) and then dissolved in tetrahydrofuran (200 ml) and ethanol (50 ml). To this solution was added hydrazine monohydrate (33.7 ml) and heated under reflux for 3 hours. The reaction mixture was cooled to room temperature, an aqueous solution of potassium carbonate was added and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. Isopropyl ether was added to the residue and filtered to remove insolubles. The filtrate was concentrated to obtain 4-methoxymethoxybenzyloxyamine (28.9 g, yield 58%) as a colorless oil. The reaction mixture was concentrated In order to remove triphenylphosphine oxide to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction The crystals were washed with ethyl acetate-hexane (1:5 v/v) and then dissolved in tetrahydrofuran (200 ml) To this solution was added hydrazine monohydrate (33.7 ml) heated under reflux for 3 hours an aqueous solution of potassium carbonate was added extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated Isopropyl ether was added to the residue filtered to remove insolubles The filtrate was concentrated

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

Procedure: Diethyl azodicarboxylate (40% toluene solution, 142 g) was added dropwise to a solution of 4-methoxymethoxybenzylalcohol (50.0 g), N-hydroxyphthalimide (44.1 g) and triphenylphosphine (83.7 g) in tetrahydrofuran (900 ml) at room temperature and stirred for 1 hour. The reaction mixture was concentrated. In order to remove triphenylphosphine oxide, the residue was subjected to silica gel chromatography to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction. The crystals were washed with ethyl acetate-hexane (1:5, v/v) and then dissolved in tetrahydrofuran (200 ml) and ethanol (50 ml). To this solution was added hydrazine monohydrate (33.7 ml) and heated under reflux for 3 hours. The reaction mixture was cooled to room temperature, an aqueous solution of potassium carbonate was added and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. Isopropyl ether was added to the residue and filtered to remove insolubles. The filtrate was concentrated to obtain 4-methoxymethoxybenzyloxyamine (28.9 g, yield 58%) as a colorless oil. The reaction mixture was concentrated In order to remove triphenylphosphine oxide to obtain crystals from an ethyl acetate-hexane (1:5, v/v)-eluted fraction The crystals were washed with ethyl acetate-hexane (1:5 v/v) and then dissolved in tetrahydrofuran (200 ml) To this solution was added hydrazine monohydrate (33.7 ml) heated under reflux for 3 hours an aqueous solution of potassium carbonate was added extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated Isopropyl ether was added to the residue filtered to remove insolubles The filtrate was concentrated

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

Procedure: Chloromethyl methyl ether (34.2 ml) was added to a mixture of 4-hydroxybenzaldehyde (50.0 g), potassium carbonate (84.9 g) and N,N-dimethylformaldehyde (150 ml) at 0° C. and stirred at room temperature for 11 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was dissolved in tetrahydrofuran (300 ml) and methanol (50 ml) and sodium borohydride (7.76 g) was added in portions at 0° C. After stirring for 30 minutes, water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was subjected to silica gel chromatography to obtain 4-methoxymethoxybenzylalcohol (56.7 g, yield 82%) as a colorless oil from an ethyl acetate-hexane (2:3, v/v) eluted fraction. extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated The residue was dissolved in tetrahydrofuran (300 ml) methanol (50 ml) and sodium borohydride (7.76 g) was added in portions at 0° C After stirring for 30 minutes water was added to the reaction mixture extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated

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

Procedure: In 30 ml of N,N-dimethylformamide were dissolved 1.2 g of 4,5-dibromo-2-ethyl-3(2H)-pyridazinone and 0.88 g of 4-methoxymethoxybenzyl alcohol, and 0.34 g of powdery potassium hydroxide was added thereto. The reaction mixture was stirred overnight at room temperature, poured into water and extracted with benzene. The benzene layer was washed with water, dried over anhydrous sodium sulfate and freed of the benzene by distillation under reduced pressure. The resulting oil was purified by means of TLC [eluting with benzene/ethyl acetate (12/1)] and recrystallization (from benzene/n-hexane) to obtain 450 mg of the aimed compound, m.p. 104°~106.0° C. was added extracted with benzene The benzene layer was washed with water dried over anhydrous sodium sulfate freed of the benzene by distillation under reduced pressure The resulting oil was purified by means of TLC [eluting with benzene/ethyl acetate (12/1)] and recrystallization (from benzene/n-hexane)