2-hydroxy-4-(methoxymethoxy)benzaldehyde

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

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

Procedure: Oven-dried potassium carbonate (0.272 g, 2 mmol) was added to a solution of 2-hydroxy-4-methoxymethyloxy-benzaldehyde (0.182 g, 1 mmol) in 10 mL of acetonitrile and the mixture was stirred for one hour at RT. Benzylbromide (0.24 mL, 2 mmol) was added and the mixture was refluxed for 10 hours. After disappearance of 2-hydroxy-4-methoxymethy-benzaldehyde (TLC), the solvent was evaporated. The residue was chromatographed over silica using hexanes:EtOAC (5:1). The organic fractions were evaporated to obtain 0.218 g (80%) of yellow oil; TLC Rf0.27 hexanes:EtOAc (5:1), 1H NMR (400 MHz, CDCl3) δ 10.4 (s, 1H, CHO); 7.81-7.83 (d, 1H, J=8.4 Hz, Ar—H6); 7.46-7.39 (m, 5H, C6H5); 6.7-6.69 (m, 2H, Ar—H3/Ar—H5); 5.21 (s, 2H, O—CH2—O); 5.16 (s, 2H, PhCH2); 3.48 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3) δ 188.6, 163.9, 162.9, 136.1, 130.5, 128.9, 128.5, 127.6, 120.2, 108.8, 101, 94.4, 70.7; analysis calc'd. for C16H16O4: C, 70.57; H, 5.92; O, 23.5. found: C, 70.35; H, 5.95; O, 23.72. the mixture was refluxed for 10 hours After disappearance of 2-hydroxy-4-methoxymethy-benzaldehyde (TLC), the solvent was evaporated The residue was chromatographed over silica The organic fractions were evaporated

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

Procedure: Oven-dried potassium carbonate (0.272 g, 2 mmol) was added to a solution of 2-hydroxy-4-methoxymethyloxy-benzaldehyde (0.182 g, 1 mmol) in 10 mL of acetonitrile and the mixture was stirred for one hour at RT. Benzylbromide (0.24 mL, 2 mmol) was added and the mixture was refluxed for 10 hours. After disappearance of 2-hydroxy-4-methoxymethy-benzaldehyde (TLC), the solvent was evaporated. The residue was chromatographed over silica using hexanes:EtOAC (5:1). The organic fractions were evaporated to obtain 0.218 g (80%) of yellow oil; TLC Rf0.27 hexanes:EtOAc (5:1), 1H NMR (400 MHz, CDCl3) δ 10.4 (s, 1H, CHO); 7.81-7.83 (d, 1H, J=8.4 Hz, Ar—H6); 7.46-7.39 (m, 5H, C6H5); 6.7-6.69 (m, 2H, Ar—H3/Ar—H5); 5.21 (s, 2H, O—CH2—O); 5.16 (s, 2H, PhCH2); 3.48 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3) δ 188.6, 163.9, 162.9, 136.1, 130.5, 128.9, 128.5, 127.6, 120.2, 108.8, 101, 94.4, 70.7; analysis calc'd. for C16H16O4: C, 70.57; H, 5.92; O, 23.5. found: C, 70.35; H, 5.95; O, 23.72. the mixture was refluxed for 10 hours After disappearance of 2-hydroxy-4-methoxymethy-benzaldehyde (TLC), the solvent was evaporated The residue was chromatographed over silica The organic fractions were evaporated

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

Procedure: Oven-dried potassium carbonate (1.38 g, 10 mmol) was added to an ice cooled solution of 2,4-dihydroxy-benzaldehyde (1.38 g, 10 mmol) in 10 mL of acetone. MOMCl (1.54 mL, 20 mmol) was added drop-wise and the mixture was stirred at 0° C. for one hour, after which it was gradually allowed to come to RT. The reaction was further stirred for 24 hours at RT and then poured into ice water with vigorous stirring. A Buff colored solid precipitated. The solid was filtered, dried and recrystallized from MeOH:DCM (ca. 30:5 mL) to obtain 1.31 g (72%) of white solid: mp 52-53° C. [Lit.(65) 50-51° C.]; TLC Rf0.43 in hexanes:EtOAc (2:1), 1H NMR (400 MHz, CDCl3) δ 11.38 (s, 1H, OH), 9.74 (s, 1H, CHO), 7.46-7.44 (d, 1H, J=8.4 Hz, Ar—H6), 6.66-6.64 (dd, 1H, 2J=8.4 Hz, 3J=2 Hz, Ar—H5), 6.60 (d, 1H, 3J=2 Hz), 5.24 (s, 2H, O—CH2—O), 3.48 (s, 3H, OCH3). 13C NMR (100 MHz, CDCl3) δ 194.8, 164.5, 164.4, 135.6, 116.2, 109.3, 103.6, 94.3, 56.7. to come to RT The reaction was further stirred for 24 hours at RT precipitated The solid was filtered dried recrystallized from MeOH

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: K2CO3 (835 mg) was suspended in dioxane (40 mL), and 2-hydroxy-4-(methoxymethoxy)benzaldehyde (1 g) and 3-methyl 2-butanal (0.787 mL) were added thereto, followed by stirring at 110° C. overnight. EtOAc was added thereto, the insoluble materials were removed by filtration through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (automatic purification device, hexane:EtOAc=95:5 to 70:30) to obtain 7-(methoxymethoxy)-2,2-dimethyl-2H-chromene-3-carbaldehyde (320 mg) as a yellow oil. the insoluble materials were removed by filtration through celite the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (automatic purification device, hexane:EtOAc=95:5 to 70:30)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: K2CO3 (835 mg) was suspended in dioxane (40 mL), and 2-hydroxy-4-(methoxymethoxy)benzaldehyde (1 g) and 3-methyl 2-butanal (0.787 mL) were added thereto, followed by stirring at 110° C. overnight. EtOAc was added thereto, the insoluble materials were removed by filtration through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (automatic purification device, hexane:EtOAc=95:5 to 70:30) to obtain 7-(methoxymethoxy)-2,2-dimethyl-2H-chromene-3-carbaldehyde (320 mg) as a yellow oil. the insoluble materials were removed by filtration through celite the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (automatic purification device, hexane:EtOAc=95:5 to 70:30)

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

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

Procedure: To a suspension of 2,4-dihydroxybenzaldehyde (0.83 g) and cesium carbonate (1.7 g) in acetonitrile (30 mL) was added chloromethyl methyl ether (0.55 mL), and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=4/1) to give 2-hydroxy-4-(methoxymethyloxy)benzaldehyde (0.84 g). the mixture was extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=4/1)

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

Procedure: To a suspension of 2,4-dihydroxybenzaldehyde (0.83 g) and cesium carbonate (1.7 g) in acetonitrile (30 mL) was added chloromethyl methyl ether (0.55 mL), and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gal (eluent: hexane/ethyl acetate=4/1) to give 2-hydroxy-4-(methoxymethyloxy)benzaldehyde (0.84 g). the mixture was extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gal (eluent: hexane/ethyl acetate=4/1)

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

Procedure: A mixture of 2-hydroxy-4-methoxymethoxybenzaldehyde (17.1 g), benzyl bromide (19.33 g), anhydrous potassium carbonate (13.0 g) and N,N-dimethylformamide (200 mL) was stirred at room temperature for 15 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was subjected to silica gel column chromatography to give 2-benzyloxy-4-methoxymethoxybenzaldehyde as a colorless oil (25.3 g, 99%) from a fraction eluted with ethyl acetate-hexane (1:4, v/v). extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate concentrated

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

Procedure: To a suspension of 2,4-dihydroxybenzaldehyde (0.83 g) and cesium carbonate (1.7 g) in acetonitrile (30 mL) was added chloromethyl methyl ether (0.55 mL), and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gal (eluent: hexane/ethyl acetate=4/1) to give 2-hydroxy-4-(methoxymethyloxy)benzaldehyde (0.84 g). the mixture was extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gal (eluent: hexane/ethyl acetate=4/1)

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

Procedure: Oven-dried potassium carbonate (0.272 g, 2 mmol) was added to a solution of 2-hydroxy-4-methoxymethyloxy-benzaldehyde (0.182 g, 1 mmol) in 10 mL of acetonitrile and the mixture was stirred for one hour at RT. Benzylbromide (0.24 mL, 2 mmol) was added and the mixture was refluxed for 10 hours. After disappearance of 2-hydroxy-4-methoxymethy-benzaldehyde (TLC), the solvent was evaporated. The residue was chromatographed over silica using hexanes:EtOAC (5:1). The organic fractions were evaporated to obtain 0.218 g (80%) of yellow oil; TLC Rf0.27 hexanes:EtOAc (5:1), 1H NMR (400 MHz, CDCl3) δ 10.4 (s, 1H, CHO); 7.81-7.83 (d, 1H, J=8.4 Hz, Ar—H6); 7.46-7.39 (m, 5H, C6H5); 6.7-6.69 (m, 2H, Ar—H3/Ar—H5); 5.21 (s, 2H, O—CH2—O); 5.16 (s, 2H, PhCH2); 3.48 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3) δ 188.6, 163.9, 162.9, 136.1, 130.5, 128.9, 128.5, 127.6, 120.2, 108.8, 101, 94.4, 70.7; analysis calc'd. for C16H16O4: C, 70.57; H, 5.92; O, 23.5. found: C, 70.35; H, 5.95; O, 23.72. the mixture was refluxed for 10 hours After disappearance of 2-hydroxy-4-methoxymethy-benzaldehyde (TLC), the solvent was evaporated The residue was chromatographed over silica The organic fractions were evaporated