4-(2-methoxyethyl)phenol

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: p-(2-Methoxyethyl)phenol (A) and epichlorohydrin (B, 1.4-2.0 eqv.) are reacted in water, at least 1.5 kg, preferably about 2 kg of water per kg of phenol, during the addition of sodium (or potassium) hydroxide solution, (1.3-1.7 eqv.) to form 1-(2,3-epoxypropoxy)-4-(2-methoxyethyl)benzene; (p-methoxyethyl-epoxypropoxybenzene). The reaction is preferably performed at a temperature of 50-70° C.

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

Procedure: a mixture of 4-(2-methoxy ethyl) phenol (1.547 g, 10.3 mmol), propiolic acid tert-butyl ester (1.367 g, 10.8 mmol) and N-methyl morpholine (1.18 mL, 10.8 mmol) in CH2Cl2 (15 mL) was stirred at room temperature for 24 hours. The mixture was absorbed on SiO2 (20 g) and purified by column chromatography using a mixture of methylene chloride/hexane. The product was obtained as a two to one mixture of (E)/(Z)-tert-butyl 3-(4-(2-methoxyethyl)phenoxy)acrylate isomers (2.0 g). The mixture was absorbed on SiO2 (20 g) purified by column chromatography a mixture of methylene chloride/hexane

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

Procedure: a mixture of 4-(2-methoxy ethyl)phenol (1.547 g, 10.3 mmol), propiolic acid tert-butyl ester (1.367 g, 10.8 mmol) and N-methyl morpholine (1.18 mL, 10.8 mmol) in CH2Cl2 (15 mL) was stirred at room temperature for 24 hours. The mixture was absorbed on SiO2 (20 g) and purified by column chromatography using a mixture of methylene chloride/hexane. The product was obtained as a two to one mixture of (E)/(Z)-tert-butyl 3-(4-(2-methoxyethyl)phenoxy)acrylate isomers (2.0 g). The mixture was absorbed on SiO2 (20 g) purified by column chromatography a mixture of methylene chloride/hexane

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

Procedure: a mixture of 4-(2-methoxy ethyl)phenol (1.547 g, 10.3 mmol), propiolic acid tert-butyl ester (1.367 g, 10.8 mmol) and N-methyl morpholine (1.18 mL, 10.8 mmol) in CH2Cl2 (15 mL) was stirred at room temperature for 24 hours. The mixture was absorbed on SiO2 (20 g) and purified by column chromatography using a mixture of methylene chloride/hexane. The product was obtained as a two to one mixture of (E)/(Z)-tert-butyl 3-(4-(2-methoxyethyl)phenoxy)acrylate isomers (2.0 g). The mixture was absorbed on SiO2 (20 g) purified by column chromatography a mixture of methylene chloride/hexane

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

Procedure: The procedure of Example 2 was repeated with a solution of 2.00 g (10.2) mmol) 4-hydroxyphenylglyoxal dimethyl acetal in 10 g methanol containing 0.37 g (10.2 mmol) hydrogen chloride and a 0.20 g dry 10% Pd/C catalyst being reacted with hydrogen gas pressurized at 50 psig at 25° C. A 47% yield of 4-(2'-methoxyethyl)phenol was obtained. a 0.20 g dry 10% Pd/C catalyst being reacted with hydrogen gas pressurized at 50 psig at 25° C

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

Procedure: The procedure of Example 2 was repeated with a solution of 2.00 g (10.2) mmol) 4-hydroxyphenylglyoxal dimethyl acetal in 10 g methanol containing 0.37 g (10.2 mmol) hydrogen chloride and a 0.20 g dry 10% Pd/C catalyst being reacted with hydrogen gas pressurized at 50 psig at 25° C. A 47% yield of 4-(2'-methoxyethyl)phenol was obtained. a 0.20 g dry 10% Pd/C catalyst being reacted with hydrogen gas pressurized at 50 psig at 25° C

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

Procedure: The procedure of Example 2 was repeated with a solution of 3.00 g (15.3 mmol) 4-hydroxyphenylglyoxal dimethyl acetal in 10 g methanol containing 0.16 g (4.4 mmol) hydrogen chloride and 0.15 g moist 10% Pd/C catalyst being reacted with hydrogen gas pressurized at 300 psig at 50° C. 300 rpm. A 59% yield of 4-(2'-methoxyethyl)phenol was obtained. pressurized at 300 psig at 50° C

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

Procedure: The procedure of Example 2 was repeated with a solution of 2.00 g (10.2 mmol) 4-hydroxyphenylglyoxal dimethyl acetal in 10 g methanol containing 0.23 g (6.3) mmol) hydrogen chloride and 0.20 g moist 10% Pd/C catalyst being reacted with hydrogen ga pressurized at 170 psig at 25° C. with stirring of 550 rpm. A 53% yield of 4-(2'-methoxyethyl)phenol was obtained. pressurized at 170 psig at 25° C.

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

Procedure: 2-Hydroxy-3-[4-(2-methoxyethyl)phenoxy]-2-methyl-N-(2-methyl-3-nitrophenyl)propionamide was prepared as described in Example 1 starting from 4-methoxyethylphenol and 2-methyloxirane-2-carboxylic acid (2-methyl-3-nitrophenyl)amide. The crude product was purified by flash chromatography (dichloromethane-2% methanol). 1H NMR (400 MHz, DMSO-d6): 1.44 (3H, s), 2.28 (3H, s), 2.72 (2H, t, J=6.8 Hz), 3.22 (3H, s), 3.47 (2H, t, J=6.8 Hz), 3.94 (1H, d, J=9.4 Hz), 4.15 (1H, d, J=9.4 Hz), 6.11 (1H, s), 6.84 (2H, d, J=7.9 Hz), 7.12 (2H, d, J=7.9 Hz), 7.41-7.45 (1H, m), 7.65-7.68 (1H, m), 7.72-7.75 (1H, m), 9.71 (1H, s). The crude product was purified by flash chromatography (dichloromethane-2% methanol)

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

Procedure: 2-Hydroxy-3-[4-(2-methoxyethyl)phenoxy]-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide was prepared as described in Example 1 starting from 4-methoxyethylphenol and 2-methyloxirane-2-carboxylic acid (3-methyl-4-nitrophenyl)amide. The crude product was purified by flash chromatography (dichloromethane-1% methanol). 1H NMR (400 MHz, DMSO-d6): 1.43 (3H, s), 2.53 (3H, s), 2.71 (2H, t, J=6.8 Hz), 3.21 (3H, s), 3.45 (2H, t, J=6.8 Hz), 3.94 (1H, d, J=9.5 Hz), 4.17 (1H, d, J=9.5 Hz), 6.20 (1H, s), 6.82 (2H, d, J=7.8 Hz), 7.10 (2H, d, J=8.0 Hz), 7.89 (1H, d, J=9.0 Hz), 7.94 (1H, s), 8.03 (1H, d, J=8.8 Hz), 10.16 (1H, s). The crude product was purified by flash chromatography (dichloromethane-1% methanol)