3-methoxy-2-phenylmethoxybenzaldehyde

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:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzyl bromide (8.6 ml) was added to a stirred solution of 3-methoxysalicylaldehyde (10 g), potassium carbonate (14.76 g) and potassium iodide (0.12 g) in DMF (120 ml) under an atmosphere of argon. The reaction was heated at 70° C. for 16 hours. Water (200 ml) was added causing the precipitation of a brown oil which crystallised on cooling. The solid was filtered, washed with water, dissolved in dichloromethane and dried (MgSO4). The solvent was removed in vacuo to give an oil which crystallised on trituration with iso-hexane to give the product as an off white solid (12.85 g, 81%); NMR d (CD3SOCD3) 3.91 (s, 3H), 5.15 (s, 2H), 7.14-7.22 (m, 2H), 7.29-7.42 (m, 6H), 10.10 (t, 1H); M/z (+) 243 (MH+). the precipitation of a brown oil which crystallised on cooling The solid was filtered washed with water dissolved in dichloromethane dried (MgSO4) The solvent was removed in vacuo to give an oil which crystallised on trituration with iso-hexane

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

Procedure: A solution of 43.00 g (0.18 mole) of 2-benzyloxy-3-methoxy-benzaldehyde of Example 1 in 300 mL of absolute ethanol is treated, with stirring, with 7.56 g (0.20 mole) of sodium borohydride. The temperature rises to 50° C. After one-half hour 10 mL of acetone is added, keeping the temperature at less than 60° C. with cooling. After 15 minutes the volatiles are stripped off at reduced pressure. Ice water (500 mL) is added and the product is extracted into 600 mL of ethyl acetate. The dried (NA2SO4) solution is concentrated. The remaining oil is dissolved in 100 mL of warm ether. Petroleum ether is added to turbidity to give 37.70 g (86% yield) of pure product; mp 58°-60° C. rises to 50° C at less than 60° C. with cooling the product is extracted into 600 mL of ethyl acetate The dried (NA2SO4) solution is concentrated The remaining oil is dissolved in 100 mL of warm ether Petroleum ether is added to turbidity

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

Procedure: A solution of 43.00 g (0.18 mole) of 2-benzyloxy-3-methoxy-benzaldehyde of Example 1 in 300 mL of absolute ethanol is treated, with stirring, with 7.56 g (0.20 mole) of sodium borohydride. The temperature rises to 50° C. After one-half hour 10 mL of acetone is added, keeping the temperature at less than 60° C. with cooling. After 15 minutes the volatiles are stripped off at reduced pressure. Ice water (500 mL) is added and the product is extracted into 600 mL of ethyl acetate. The dried (NA2SO4) solution is concentrated. The remaining oil is dissolved in 100 mL of warm ether. Petroleum ether is added to turbidity to give 37.70 g (86% yield) of pure product; mp 58°-60° C. rises to 50° C at less than 60° C. with cooling the product is extracted into 600 mL of ethyl acetate The dried (NA2SO4) solution is concentrated The remaining oil is dissolved in 100 mL of warm ether Petroleum ether is added to turbidity

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

Procedure: A solution of 96.90 g (0.40 mole) of 2-benzyloxy-3-methoxybenzaldehyde, 48.04 g (0.48 mole) of hydantoin, 8.02 g (0.09 mole) of β-alanine, and 200 mL of glacial acetic acid is stirred at reflux for 6 hours. Water (500 mL) is added and the separated solid is filtered, washed well with water, methanol, and then ether; wt 109.00 g (84% yield); mp 210°-212° C. at reflux for 6 hours the separated solid is filtered washed well with water, methanol

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

Procedure: A solution of 96.90 g (0.40 mole) of 2-benzyloxy-3-methoxybenzaldehyde, 48.04 g (0.48 mole) of hydantoin, 8.02 g (0.09 mole) of β-alanine, and 200 mL of glacial acetic acid is stirred at reflux for 6 hours. Water (500 mL) is added and the separated solid is filtered, washed well with water, methanol, and then ether; wt 109.00 g (84% yield); mp 210°-212° C. at reflux for 6 hours the separated solid is filtered washed well with water, methanol

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

Procedure: A mixture of 196.0 g (1.30 mole) of o-vanillin (Aldrich), 200 g of benzyl bromide (Aldrich), 500 g of anhydrous potassium carbonate and 1,500 mL of absolute ethanol is heated, with stirring, at reflux for 6 hours. After cooling, the supernatant is decanted and the remainder is filtered. The combined filtrate and supernatant is concentrated at reduced pressure to remove solvent. The remaining oil is extracted into 1 L of ether. The ether solution is washed with 500 mL of water, 600 mL of 1% potassium hydroxide solution, and 500 mL of water and then dried (potassium carbonate) and concentrated to give 263.4 g (84% yield) of product; mp 41°-43° C. Reported mp, 43° C. (Chem. Abstr. 62:16110a). is heated at reflux for 6 hours After cooling the supernatant is decanted the remainder is filtered The combined filtrate and supernatant is concentrated at reduced pressure to remove solvent The remaining oil is extracted into 1 L of ether The ether solution is washed with 500 mL of water, 600 mL of 1% potassium hydroxide solution, and 500 mL of water dried (potassium carbonate) concentrated

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

Procedure: A mixture of 196.0 g (1.30 mole) of o-vanillin (Aldrich), 200 g of benzyl bromide (Aldrich), 500 g of anhydrous potassium carbonate and 1,500 mL of absolute ethanol is heated, with stirring, at reflux for 6 hours. After cooling, the supernatant is decanted and the remainder is filtered. The combined filtrate and supernatant is concentrated at reduced pressure to remove solvent. The remaining oil is extracted into 1 L of ether. The ether solution is washed with 500 mL of water, 600 mL of 1% potassium hydroxide solution, and 500 mL of water and then dried (potassium carbonate) and concentrated to give 263.4 g (84% yield) of product; mp 41°-43° C. Reported mp, 43° C. (Chem. Abstr. 62:16110a). is heated at reflux for 6 hours After cooling the supernatant is decanted the remainder is filtered The combined filtrate and supernatant is concentrated at reduced pressure to remove solvent The remaining oil is extracted into 1 L of ether The ether solution is washed with 500 mL of water, 600 mL of 1% potassium hydroxide solution, and 500 mL of water dried (potassium carbonate) concentrated

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

Procedure: To a well-stirred suspension of 2.0 g (52.7 mmol) of sodium borohydride in 65 mL of ethyl alcohol at 0° C. under a nitrogen atmosphere, was slowly added 15 g (61.9 mmol) of 2-benzyloxy-3-methoxybenzaldehyde, from Step 1, in 100 mL of ethyl alcohol. The reaction mixture was stirred at 0° C. for 10 minutes and then 50 mL of water was added to quench the reaction, followed by 50 mL of diethyl ether. The mixture was slowly added to 60 mL of 10% aqueous hydrochloric acid solution at 0° C. and the resultant mixture was stirred for 1 h and then extracted with 3×200 mL of diethyl ether. The combined ether extracts were washed with aqueous sodium bicarbonate solution, water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 15.14 g (100% yield) of the title compound as a white solid. to quench the reaction extracted with 3×200 mL of diethyl ether The combined ether extracts were washed with aqueous sodium bicarbonate solution, water and brine dried over anhydrous sodium sulfate filtered concentrated in vacuo

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

Procedure: A 60% dispersion of sodium hydride in mineral oil (5.26 g, 140 mmol) was washed with hexane and the hexane was removed. To the washed sodium hydride was added 75 mL of anhydrous DMF. The resultant slurry was well stirred and 21.38 g (140 mmol) of 2-hydroxy-3-methoxy benzaldehyde (commercially available from Aldrich Chemical Company) was added dropwise, over a period of 45 minutes. The mixture was stirred at 50° C. for 1 h and then 16.2 mL (140 mmol) of benzyl chloride was added in one portion. The reaction mixture was stirred at 50° C. for 3 days and then allowed to slowly (overnight) cool to ambient temperature and the reaction was quenched with 60 mL of 10% aqueous hydrochloric acid solution. The mixture was extracted with 3×250 mL of ethyl acetate and the combined ethyl acetate extracts were washed with 250 mL of aqueous sodium bicarbonate solution, water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel eluted with ethyl acetate:hexane (1:9 v/v) to give 26.39 g (77.5%) of the title compound. the hexane was removed To the washed sodium hydride was added 75 mL of anhydrous DMF The mixture was stirred at 50° C. for 1 h The reaction mixture was stirred at 50° C. for 3 days allowed to slowly (overnight) the reaction was quenched with 60 mL of 10% aqueous hydrochloric acid solution The mixture was extracted with 3×250 mL of ethyl acetate the combined ethyl acetate extracts were washed with 250 mL of aqueous sodium bicarbonate solution, water and brine dried over anhydrous sodium sulfate filtered concentrated in vacuo The residue was purified by chromatography on silica gel eluted with ethyl acetate:hexane (1:9 v/v)