2,3-dihydroxy-4-methoxybenzaldehyde

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(N,N-dimethylamino)ethyl-(3′,4′,5′-trimethoxyphenyl)ketone (4, 1.17 g, 4.37 mmol), 2,3-dihydroxy-4-methoxybenzaldehyde (2, 0.74 g, 4.37 mmol), 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide (0.12 g, 0.44 mmol) and Et3N (1 ml) was heated under reflux at 115° C. for 3.5 hours. After quenching with 1M HCl, the product was extracted with CH2Cl2. The combined extract was washed with water, rinsed with brine and dried over anhydrous magnesium sulfate. Purification was done by silica gel flash column chromatography (60:40, hexane-ethyl acetate) which afforded the pure yellow-colored phenol (0.179 g, 0.48 mmol) in 11% yield. The phenol had a melting point of 189-190° C. was heated After quenching with 1M HCl the product was extracted with CH2Cl2 The combined extract was washed with water rinsed with brine dried over anhydrous magnesium sulfate Purification

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(N,N-dimethylamino)ethyl-(3′,4′,5′-trimethoxyphenyl)ketone (4, 1.17 g, 4.37 mmol), 2,3-dihydroxy-4-methoxybenzaldehyde (2, 0.74 g, 4.37 mmol), 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide (0.12 g, 0.44 mmol) and Et3N (1 ml) was heated under reflux at 115° C. for 3.5 hours. After quenching with 1M HCl, the product was extracted with CH2Cl2. The combined extract was washed with water, rinsed with brine and dried over anhydrous magnesium sulfate. Purification was done by silica gel flash column chromatography (60:40, hexane-ethyl acetate) which afforded the pure yellow-colored phenol (0.179 g, 0.48 mmol) in 11% yield. The phenol had a melting point of 189-190° C. was heated After quenching with 1M HCl the product was extracted with CH2Cl2 The combined extract was washed with water rinsed with brine dried over anhydrous magnesium sulfate Purification

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

Procedure: 2,3,4-trimethoxybenzaldehyde, 1 (9.8 g, 50 mmol) was dissolved in anhydrous dichloromethane (150 ml) under argon at ambient temperature. It was stirred for 10 minutes and boron trichloride (100 ml, 100 mmol, 2 eq; 1.0M solution in dichloromethane) was added. The dark reaction mixture was stirred for 24 hours and then slowly poured into 10% sodium bicarbonate (aq) (40 g/360 ml). The resulting solution was acidified with concentrated hydrochloric acid to pH 1. The dichloromethane layer was separated and the aqueous layer was extracted with ethyl acetate (4×100 ml) and dried. Evaporation of the solvent in vacuo gave a brown oil which was absorbed onto silica gel and subjected to flash chromatography (70:30, hexane-ethyl acetate). The diol 2 was obtained as a pale yellow solid (6.70 g, 80%). The dark reaction mixture was stirred for 24 hours The dichloromethane layer was separated the aqueous layer was extracted with ethyl acetate (4×100 ml) dried Evaporation of the solvent in vacuo gave a brown oil which was absorbed onto silica gel

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

Procedure: 2,3,4-trimethoxybenzaldehyde, 1 (9.8 g, 50 mmol) was dissolved in anhydrous dichloromethane (150 ml) under argon at ambient temperature. It was stirred for 10 minutes and boron trichloride (100 ml, 100 mmol, 2 eq; 1.0M solution in dichloromethane) was added. The dark reaction mixture was stirred for 24 hours and then slowly poured into 10% sodium bicarbonate (aq) (40 g/360 ml). The resulting solution was acidified with concentrated hydrochloric acid to pH 1. The dichloromethane layer was separated and the aqueous layer was extracted with ethyl acetate (4×100 ml) and dried. Evaporation of the solvent in vacuo gave a brown oil which was absorbed onto silica gel and subjected to flash chromatography (70:30, hexane-ethyl acetate). The diol 2 was obtained as a pale yellow solid (6.70 g, 80%). The dark reaction mixture was stirred for 24 hours The dichloromethane layer was separated the aqueous layer was extracted with ethyl acetate (4×100 ml) dried Evaporation of the solvent in vacuo gave a brown oil which was absorbed onto silica gel

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

Procedure: To a vigorously stirred solution of sodium boratedecahydrate (borax, 30 g) in 600 mL of water was added 2,3,4-trihydroxy-benzaldehyde (5 g, 32.4 mmol). The yellow solution was stirred at room temperature for 30 min followed by dropwise and simultaneous addition (over 30 min) of sodium hydroxide (4.0 g, 100 mmol) in water (50 mL) and dimethylsulfate (9.45 mL, 100 mmol). Vigorous stirring was continued overnight and conc. hydrochloric acid was added to pH 1. After stirring for an additional 30 min the mixture was extracted with chloroform (5×300 ml). The organic layer was once washed with brine, dried and evaporated to yield a slightly yellowish solid which on crystallization from ethyl acetate-hexane afforded slightly yellowish colored needles (3.9 g, 72%), mp 116°-17° C.: (lit. 118°-119° C.), IR (film) 3374, 1646, 1505, 1461, 1443, 1278, 1210, 1106, 636 cm-1 ; 1H-NMR 3.987 (3H, s, OCH3), 5,466 (1H, brs, OH-3, D2O exchanged) 6.617 (1H, d, JAB =8.62, H-5), 7.147 (1H, d, JBA =8.62 HZ, H-6, 9,757 (1H, S, CHO) 11,113 (1H, brs, OH-2, D2O exchanged); and HREIMS (m/z, 168.0419 (M, 100%; calcd 168.0423 for C8H8O4). Vigorous stirring was continued overnight After stirring for an additional 30 min the mixture was extracted with chloroform (5×300 ml) The organic layer was once washed with brine dried evaporated to yield a slightly yellowish solid which on crystallization from ethyl acetate-hexane

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(N,N-dimethylamino)ethyl-(3′,4′,5′-trimethoxyphenyl)ketone (4, 1.17 g, 4.37 mmol), 2,3-dihydroxy-4-methoxybenzaldehyde (2, 0.74 g, 4.37 mmol), 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide (0.12 g, 0.44 mmol) and Et3N (1 ml) was heated under reflux at 115° C. for 3.5 hours. After quenching with 1M HCl, the product was extracted with CH2Cl2. The combined extract was washed with water, rinsed with brine and dried over anhydrous magnesium sulfate. Purification was done by silica gel flash column chromatography (60:40, hexane-ethyl acetate) which afforded the pure yellow-colored phenol (0.179 g, 0.48 mmol) in 11% yield. The phenol had a melting point of 189-190° C. was heated After quenching with 1M HCl the product was extracted with CH2Cl2 The combined extract was washed with water rinsed with brine dried over anhydrous magnesium sulfate Purification

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(N,N-dimethylamino)ethyl-(3′,4′,5′-trimethoxyphenyl)ketone (4, 1.17 g, 4.37 mmol), 2,3-dihydroxy-4-methoxybenzaldehyde (2, 0.74 g, 4.37 mmol), 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide (0.12 g, 0.44 mmol) and Et3N (1 ml) was heated under reflux at 115° C. for 3.5 hours. After quenching with 1M HCl, the product was extracted with CH2Cl2. The combined extract was washed with water, rinsed with brine and dried over anhydrous magnesium sulfate. Purification was done by silica gel flash column chromatography (60:40, hexane-ethyl acetate) which afforded the pure yellow-colored phenol (0.179 g, 0.48 mmol) in 11% yield. The phenol had a melting point of 189-190° C. was heated After quenching with 1M HCl the product was extracted with CH2Cl2 The combined extract was washed with water rinsed with brine dried over anhydrous magnesium sulfate Purification

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

Procedure: 2,3,4-trimethoxybenzaldehyde, 1 (9.8 g, 50 mmol) was dissolved in anhydrous dichloromethane (150 ml) under argon at ambient temperature. It was stirred for 10 minutes and boron trichloride (100 ml, 100 mmol, 2 eq; 1.0M solution in dichloromethane) was added. The dark reaction mixture was stirred for 24 hours and then slowly poured into 10% sodium bicarbonate (aq) (40 g/360 ml). The resulting solution was acidified with concentrated hydrochloric acid to pH 1. The dichloromethane layer was separated and the aqueous layer was extracted with ethyl acetate (4×100 ml) and dried. Evaporation of the solvent in vacuo gave a brown oil which was absorbed onto silica gel and subjected to flash chromatography (70:30, hexane-ethyl acetate). The diol 2 was obtained as a pale yellow solid (6.70 g, 80%). The dark reaction mixture was stirred for 24 hours The dichloromethane layer was separated the aqueous layer was extracted with ethyl acetate (4×100 ml) dried Evaporation of the solvent in vacuo gave a brown oil which was absorbed onto silica gel

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

Procedure: An anhydrous dichloromethane (50 ml) solution of 2,3,4-trimethoxybenzaldehyde (1.96 g, 10 mmol) under argon at room temperature was stirred for 10 min and boron trichloride (10 ml, 10 mmol, 1 eq; 1.0 M solution in dichloromethane) was added. After 2 h, the second equivalent of boron trichloride (10 ml, 10 mmol, 1 eq; 1.0 M solution of dichloromethane) was added. The dark reaction mixture was stirred overnight and then slowly poured into 10% sodium bicarbonate (aq) (4 g/36 ml). The resulting solution was acidified with concentrated hydrochloride acid to pH 1. The dichloromethane layer was separated, and the aqueous layer extracted with ethyl acetate (4×20 ml) and dried. Evaporation of solvent in vacuum gave brown oil, which was further separated by column chromatography (1:1 hexane-ethyl acetate) to afford a yellow solid. Recrystallization from ethyl acetate-hexane gave a pale yellow needle of 48 (1.1 g, 65.5%); Rf0.40 (hexane:ethyl acetate: 1:1). The dark reaction mixture The dichloromethane layer was separated the aqueous layer extracted with ethyl acetate (4×20 ml) dried Evaporation of solvent in vacuum gave brown oil, which was further separated by column chromatography (1:1 hexane-ethyl acetate) to afford a yellow solid Recrystallization from ethyl acetate-hexane

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

Procedure: To a solution of 21 (26.70 g, 158.7 mmol) in DMF (150 mL) under nitrogen, was added K2CO3 (65.84 g, 476.3 mmol) followed by 2-bromopropane (44.72 mL, 476.3 mmol) and heated to reflux (90° C.) for 12 hours. Water (200 mL) and EtOAc (200 mL) were added to the reaction mixture, the phases were separated, and the aqueous phase was extracted with EtOAc (3×200 mL). The combined organic solutions were dried over MgSO4 and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, elution with hexane) provided 32.85 g (1.30.2 mmol, 82%) of the diusopropyl-protected aldehyde 22 as a yellow oil. heated the phases were separated the aqueous phase was extracted with EtOAc (3×200 mL) The combined organic solutions were dried over MgSO4 concentrated under reduced pressure Purification by flash column chromatography (silica gel, elution with hexane)

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

Procedure: A dry CH2Cl2 (200 mL) solution of 2,3,4-trimethoxybenzaldehyde (19.6 g, 100 mmol), under nitrogen, was stirred for 10 min and BCl3 (1.0M solution in CH2Cl2, 200 mL) was added. The reaction was stirred for 24 hours and a 10% sodium bicarbonate solution (40 g/360 mL) was added. The resulting solution was acidified with concentrated HCl to PH 1. The organic layer was separated, and the aq. layer was extracted with EtOAc (4×100 mL). The organic layer was dried with MgSO4 and filtered through celite. After solvent evaporation, the crude mixture was recrystallized using (Hexanes/EtOAc:70/30) to afford 12.2 g (72.6 mmol, 73%) of a purple solid. The organic layer was separated the aq. layer was extracted with EtOAc (4×100 mL) The organic layer was dried with MgSO4 filtered through celite After solvent evaporation the crude mixture was recrystallized

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

Procedure: An anhydrous dichloromethane (50 ml) solution of 2,3,4-trimethoxybenzaldehyde (1.96 g, 10 mmol) under argon at room temperature was stirred for 10 min and boron trichloride (10 ml, 10 mmol, 1 eq; 1.0 M solution in dichloromethane) was added. After 2 h, the second equivalent of boron trichloride (10 ml, 10 mmol, 1 eq; 1.0 M solution of dichloromethane) was added. The dark reaction mixture was stirred overnight and then slowly poured into 10% sodium bicarbonate (aq) (4 g/36 ml). The resulting solution was acidified with concentrated hydrochloride acid to pH 1. The dichloromethane layer was separated, and the aqueous layer extracted with ethyl acetate (4×20 ml) and dried. Evaporation of solvent in vacuum gave brown oil, which was further separated by column chromatography (1:1 hexane-ethyl acetate) to afford a yellow solid. Recrystallization from ethyl acetate-hexane gave a pale yellow needle of 48 (1.1 g, 65.5%); Rf0.40 (hexane:ethyl acetate: 1:1). The dark reaction mixture The dichloromethane layer was separated the aqueous layer extracted with ethyl acetate (4×20 ml) dried Evaporation of solvent in vacuum gave brown oil, which was further separated by column chromatography (1:1 hexane-ethyl acetate) to afford a yellow solid Recrystallization from ethyl acetate-hexane