(3,4-dimethoxyphenyl)methanol

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

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

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

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

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

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

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

Procedure: A dimethyl sulfoxide solution of 4.29 ml (30 mmol) veratryl alcohol (3,4-dimethoxybenzyl alcohol) was treated in 22.86 ml (180 mmol) trimethylsilyl chloride at room temperature for 1 hour. The resulting product was dissolved in ethyl acetate, washed with distilled water and saturated brine, and dried over anhydrous magnesium sulfate. After concentration under vacuum, the resulting residue was reacted with 2.14 g (10 mmol) of 4-benzylideneamino-5-imidazole carboxamide and 5.52 (40 mmol) of potassium carbonate in the same manner as in Reference Example 2 to obtain 1.73 g of 4-amino-1-(3,4-dimethoxybenzyl)-5-imidazolecarboxamide (yield 63%). washed with distilled water and saturated brine dried over anhydrous magnesium sulfate After concentration under vacuum

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

Procedure: 22 ml of a dipotassium hydrogen phosphate/citric acid buffer solution of pH 4.5 (prepared by titrating a 0.2 M potassium dihydrogen phosphate solution with a 0.1 M citric acid solution and diluting to ¼) were treated at 45° C. with 243 mg (1.60 mmol) of 3,4-dimethoxytoluene in 1 ml of ethanol. 0.180 minmol of a mediator (Table 1) was added with stirring. After approx. 10 minutes, the mixture was treated with 5 ml of an aqueous solution of 2 mg/ml laccase from Trametes versicolor (specific activity: approx. 18 IU/mg, defined with ABTS as substrate). After a reaction time of 22 hours with exposure to air, the reaction solution was extracted with chloroform and examined by NMR spectroscopy and gas chromatography. Yields of 3,4-dimethoxybenzaldehyde and 3,4dimethoxybenzyl alcohol, see Table 1. diluting to ¼) 0.180 minmol of a mediator (Table 1) was added After a reaction time of 22 hours with exposure to air, the reaction solution was extracted with chloroform

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

Procedure: 22 ml of a dipotassium hydrogen phosphate/citric acid buffer solution of pH 4.5 (prepared by titrating a 0.2 M potassium dihydrogen phosphate solution with a 0.1 M citric acid solution and diluting to 1/4) were treated at 45° C. with 243 mg (1.60 mmol) of 3,4-dimethoxytoluene in 1 ml of ethanol. 0.180 mmol of a mediator (Table 1) was added with stirring. After approx. 10 minutes, the mixture was treated with 5 ml of an aqueous solution of 2 mg/ml laccase from Trametes versicolor (specific activity: approx. 18 IU/mg, defined with ABTS as substrate). After a reaction time of 22 hours with exposure to air, the reaction solution was extracted with chloroform and examined by N spectroscopy and gas chromatography. Yields of 3,4-dimethoxybenzaldehyde and 3,4-dimethoxybenzyl alcohol, see Table 1. diluting to 1/4) 0.180 mmol of a mediator (Table 1) was added After a reaction time of 22 hours with exposure to air, the reaction solution was extracted with chloroform

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

Procedure: 3,4-dimethoxybenzyl alcohol (20 g, 119 mmol) was dissolved in toluene (60 ml) and cooled to 0° C. Thionyl chloride (7.48 g, 61.4 mmol) was added dropwise to the cooled solution of the alcohol over a period of 30 minutes, and the reaction was maintained at 0° C. for an additional 30 minutes. The reaction was quenched by pouring onto an ice/water mix (100 ml), and the organic phase was separated. The aqueous phase was then extracted into toluene (2×20 ml) and the combined toluene solution was dried over anhydrous sodium sulfate. The toluene was removed at reduced pressure to afford an oil which solidified upon standing, with a yield of 21 g. The material was characterized as a single spot by thin layer chromatography (TLC). the reaction was maintained at 0° C. for an additional 30 minutes The reaction was quenched by pouring onto an ice/water mix (100 ml) the organic phase was separated The aqueous phase was then extracted into toluene (2×20 ml) the combined toluene solution was dried over anhydrous sodium sulfate The toluene was removed at reduced pressure to afford an oil which

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

Procedure: Sodium hydride (80% disp. in oil; 933 mg, 31.1 mmol) was added, all at once to 3,4-dimethoxybenzyl alcohol (3.48 g, 20.7 mmol) in DMF (40 mL) at 0° C. and under Ar. After 5 min., the mixture was allowed to warm to r.t. After 1 h, 1-bromo-3,5-difluorobenzene (4 g, 20.7 mmol) in DMF (5 mL) was added dropwise at r.t. The resulting mixture was kept at this temperature for 16 h and slowly poured into H2O (500 mL). It was extracted with EtOAc (3×) and the combined organics were washed with 25% NH4OAc buffer (1×), H2O (2×) and brine. The solution was dried (MgSO4) and concentrated to give a pale yellow solid that was purified by column chromatography on silica gel (EtOAc:hexane, 10:90-15:85) to afford the title compound as a white solid (5.85 g, 83%). at 0° C. After 1 h The resulting mixture was kept at this temperature for 16 h It was extracted with EtOAc (3×) the combined organics were washed with 25% NH4OAc buffer (1×), H2O (2×) and brine The solution was dried (MgSO4) concentrated to give a pale yellow solid that was purified by column chromatography on silica gel (EtOAc:hexane, 10:90-15:85)

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

Procedure: Sodium hydride (80% disp. in oil; 933 mg, 31.1 mmol) was added, all at once to 3,4-dimethoxybenzyl alcohol (3.48 g, 20.7 mmol) in DMF (40 mL) at 0° C. and under Ar. After 5 min., the mixture was allowed to warm to r.t. After 1 h, 1-bromo-3,5-difluorobenzene (4 g, 20.7 mmol) in DMF (5 mL) was added dropwise at r.t. The resulting mixture was kept at this temperature for 16 h and slowly poured into H2O (500 mL). It was extracted with EtOAc (3×) and the combined organics were washed with 25% NH4OAc buffer (1×), H2O (2×) and brine. The solution was dried (MgSO4) and concentrated to give a pale yellow solid that was purified by column chromatography on silica gel (EtOAc:hexane, 10:90-15:85) to afford the title compound as a white solid (5.85 g, 83%). at 0° C. After 1 h The resulting mixture was kept at this temperature for 16 h It was extracted with EtOAc (3×) the combined organics were washed with 25% NH4OAc buffer (1×), H2O (2×) and brine The solution was dried (MgSO4) concentrated to give a pale yellow solid that was purified by column chromatography on silica gel (EtOAc:hexane, 10:90-15:85)