3-Benzyloxyphenol

White solid

To a mixture of A-14 (4.0 g, 36.4 mmol) in Acetone (50 mL) with KPreparation 55. 3-Benzyloxy phenol; Benzene-l, 3-diol (10.0 grams, 90.9 mmol), dissolved in acetone (50 mL), was cooled to 5-10 0C, and added with anhydrous potassium carbonate (18.8 grams, 136.3 mol) under smooth stirring. Benzyl bromide (10.88 grams, 63.6 mmol) was slowly introduced to the reaction mass at this temperature and cooling bath was removed after ten minutes. The reaction mixture was refiuxed for 12 to 17 hours. After bringing to 20 to 40 °C, the solid potassium carbonate was filtered out. The filtrate was concentrated and poured over ice-water, acidified with 6 N hydrochloric acid and extracted with ethyl acetate (3x25 mL). The combined organic layer was washed with water, dried with anhydrous sodiumsulphate and evaporated to get brown colored gummy mass. The dibenzyloxy bye-product was discarded by column chromatographic purification using 230-400 mesh silica-gel and mixture of ethyl acetate and petroleum ether (10:90) to yield pure a light brown gummy mass title compound. Yield: 13.5 g, 68percent 1H NMR (CDCl3, 200 MHz): δ 7.50-7.30 (m, 5H), 7.12 (t, J = 8.2 Hz, IH), 6.57 (dd, J = 1.8 6.2 Hz, IH), 6.50-6.40 (m, 2H), 5.02 (s, 2H), 4.86 (bs, IH, D2O exchangeable). Mass (CI): m/z 201(M++l). IR (cm'1) (KBr): 3406, 3032, 1595, 1490, 1454.Preparation Example 18. C-(5-(3-Benzyloxy-phenoxy)-thiophen-2-yl)-methylamine To a solution of resorcinol (10g, 90.8mmol) in N, N-dimethylformamide (100mL) was added potassium carbonate (12.6g, 90.8mmol) and benzyl bromide (10.8mL, 90.8mmol), and the mixture was stirred at 60°C for 2 hours. The reaction mixture was allowed to room temperature, ethyl acetate and water were added for partitioning, the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated, then, the residue was purified by silica gel column chromatography (hexane : ethyl acetate), and 3-benzyloxy-phenol (6.0g, 33percent) was obtained as a pale brown oil. To a solution of the resulting 3-benzyloxy-phenol (2.6g, 13.0mmol) and a 5-nitrothiophene-2-carbonitrile (2.0g, 13.0mmol) in dimethylsulfoxide (25mL) was added potassium carbonate (1.98g, 14.0mmol), and the solution was stirred at 70°C for 3 hours. The reaction solution was allowed to room temperature, ethyl acetate and water were added for partitioning, the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated, the residue was purified by silica gel column chromatography (hexane : ethyl acetate = 10 : 1), and 5-(3-benzyloxy-phenoxy)-thiophene-2-carbonitrile (110mg, 2.8percent) was obtained as a pale brown solid. Next, to a solution of lithium aluminum hydride (27mg, 0.716mmol) in tetrahydrofuran (2.0mL) was added a solution of 5-(3-benzyloxy-phenoxy)-thiophene-2-carbonitrile obtained above (110mg, 0.358mmol) in tetrahydrofuran (1mL), and the solution was stirred at room temperature for 3 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was evaporated to obtain the title compound (80mg, 72percent) as a red solid. This compound was used in the next reaction without purification.To a solution of resorcinol (10g, 90.8mmol) in N, N-dimethylformamide (100mL) was added potassium carbonate (12.6g, 90.8mmol) and benzyl bromide (10.8mL, 90.8mmol), and the mixture was stirred at 60°C for 2 hours. The reaction mixture was allowed to room temperature, ethyl acetate and water were added for partitioning, the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated, then, the residue was purified by silica gel column chromatography (hexane : ethyl acetate), and 3-benzyloxy-phenol (6.0g, 33percent) was obtained as a pale brown oil. To a solution of the resulting 3-benzyloxy-phenol (2.6g, 13.0mmol) and a 5-nitrothiophene-2-carbonitrile (2.0g, 13.0mmol) in dimethylsulfoxide (25mL) was added potassium carbonate (1.98g, 14.0mmol), and the solution was stirred at 70°C for 3 hours. The reaction solution was allowed to room temperature, ethyl acetate and water were added for partitioning, the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated, the residue was purified by silica gel column chromatography (hexane : ethyl acetate = 10 : 1), and 5-(3-benzyloxy-phenoxy)-thiophene-2-carbonitrile (110mg, 2.8percent) was obtained as a pale brown solid. Next, to a solution of lithium aluminum hydride (27mg, 0.716mmol) in tetrahydrofuran (2.0mL) was added a solution of 5-(3-benzyloxy-phenoxy)-thiophene-2-carbonitrile obtained above (110mg, 0.358mmol) in tetrahydrofuran (1mL), and the solution was stirred at room temperature for 3 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was evaporated to obtain the title compound (80mg, 72percent) as a red solid. This compound was used in the next reaction without purification.3-Benzyloxy-phenol (JRL01015) b b Resorcinol (11 g, 100 mmol) was dissolved in acetone (100 mL). To this solution, powdered potassium carbonate (13.8 g, 300 mmol) and potassium iodide (pinch) were added slowly. The mixture was refluxed and benzyl chloride (11.6 mL, 100 mmol) added drop wise to the refluxing mixture over a period of 30 min. The reaction was carried at for 48 h and cooled the reaction to room temperature and potassium carbonate was filtered and washed with acetone, the collected filtrates concentrated by vacuum distillation. Product thus obtained was purified by column chromatography using chloroform and hexane (3:7) mixture as eluent to yield pale brown color solid (12 g; 72percent).

Molecular Weight:200.23
XLogP3:3.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:200.083729621
Monoisotopic Mass:200.083729621
Topological Polar Surface Area:29.5
Heavy Atom Count:15
Complexity:175
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes