methyl 4-(4-hydroxybutyl)benzoate

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: To mixture of 4.19 g (1.5 eq) of pyridinium chlorochromate and 1.76 g (1.0 eq) of sodium acetate in 100 mL of dry methylene chloride are added, under nitrogen and with stirring, 2.70 g 1.0 eq) of methyl 4-(4-hydroxybutyl)benzoate in 50 mL of dry methylene chloride. The reaction mixture is stirred 12 hours, diluted with diethyl ether, and filtered. After concentration at reduced pressure, the residue is distilled under vacuum to yield 4-(4-carbomethoxyphenyl)-butanal as an oil, b.p. 131° C. at <1 torr; IR (film) νmax 2950, 2720, 1722, 1612, 1285, and 1110 cm-1 ; 1H NMR (CDCl3) delta 9.77 (m, 1H, --CHO), 7.98 (d, J=9 Hz, 2H, Ar), 7.24 (d, J=8.2 Hz, 2H, Ar), 3.90 (s, 3H, --CH3), 2.72 (t, 2H, benzyl), 2.47 (mm, 2H, --CH2CHO), 1.95 (m, 2H, --CH2). are added, under nitrogen The reaction mixture is stirred 12 hours filtered After concentration at reduced pressure the residue is distilled under vacuum

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

Procedure: A mixture of 2.55 g of methyl 4-(4-hydrox-but-1-yn-1-yl)benzoate in 200 mL of ethanol is hydrogenated at 50 psi of hydrogen for 12 hours in the presence of 0.26 g (10% weight equivalent) of 5% palladium on charcoal. The reaction mixture is filtered through a silica gel pad, which is washed with ethanol, and concentrated to yield methyl 4-(4-hydroxybutyl)benzoate as an oil. IR (film) νmax 3390, 2965, 2920, 2850, 1705, 1605, 1568, 1520, 1500, 1410, 1387, 1362, 1308, 1286, 1250, 1160, 1055, 1013, 843, 755, and 695 cm-1 ; 1H NMR (CDCl3) delta 7.95 (d, J=8.1 Hz, 2H, Ar), 7.25 (d, J=8.1 Hz, 2H, Ar), 3.89 (s, 3H, --CH3), 3.65 (t, J=6.3 Hz, 2H, --CH2OH), 2.69 (t, J=7.5 Hz, 2H, benzyl), 1.66 (m, 4H, 2° aliphatic). The reaction mixture is filtered through a silica gel pad, which is washed with ethanol concentrated

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

Procedure: To a mixture of 0.082 g (0.005 eq) of palladium chloride, and 0.244 g (0.01 eq) of triphenylphosphine, and 20.00 g (1.0 eq) of methyl 4-bromobenzoate in diethylamine which is stirred under nitrogen is added 0.178 g (0.01 eq) of copper (I) iodide and 6.52 g (1.0 eq) of 3-butyn-1-ol. The reaction mixture is stirred under nitrogen at room temperature (about 25° C.) for eighteen hours. Diethylamine is then removed under reduced pressure, water is added, and the mixture extracted with benzene. The benzene extracts are filtered through silica to remove the metal residue and the filtrate concentrated under reduced pressure to yield methyl 4-(4-hydroxybut-1-yl)benzoate. Recrystallization from a mixture of benzene and hexane yields pure material in 75.8% yield, m.p. 95.5°-96.0° C.; IR (KBr) νmax 3310, 2955, 1718, 1604, 1433, 1275, 1177, 1108, 1040, 955, 852, and 769 cm-1 ; 1H NMR (CDCl3) delta 7.98 (d, J=8.3 Hz, 2H, Ar), 7.49 (d, J=8.3 Hz, 2H, Ar), 3.93 (s, 3H, --CH3), 3.87 (m, 2H, --CH2OH), 2.74 (t, J=6.2 Hz, 2H, --yl--CH2 --), 1.88 (m, 1H, --OH). The reaction mixture is stirred under nitrogen at room temperature (about 25° C.) for eighteen hours Diethylamine is then removed under reduced pressure, water is added the mixture extracted with benzene The benzene extracts are filtered through silica to remove the metal residue the filtrate concentrated under reduced pressure

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

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

Procedure: To a mixture of 4.97 g (23 mmol) of pyridinium chlorochromate and 1.23 g (15 mmol) of sodium acetate in 100 mL of dry methylene chloride was added 3.2 g (15.3 mmol) of methyl 4-(4-hydroxybutyl)benzoate in 50 mL of methylene chloride at room temperature. The resulting mixture was stirred at room temperature for 3 hours, diluted with 150 mL of ethyl ether, filtered through a silica gel pad, and concentrated. The residue was purified by column chromatography (silica gel/hexane:ethyl acetate=4:1) to give 2.85 g (90%) of 4-(4-methoxycarbonylphenyl)butyraldehyde as a light yellow oil: 1H NMR (CDCl3) δ 2.15-2.40 (2H, m), 2.72 (2H, t, J=6.6 Hz), 2.96 (2H, t, J=7.2 Hz), 4.15 (3H, s), 7.50 (2H, d, J=8.1 Hz), 8.21 (2H, d, J=8.1 Hz), 10.01 (1H. s); MS m/z 206 (M+), 175, 162, 131,103, 91, 63. filtered through a silica gel pad concentrated The residue was purified by column chromatography (silica gel/hexane:ethyl acetate=4:1)

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

Procedure: A Parr flask was charged with 3.25 g (15.98 mmol) of methyl 4-(4-hydroxy-1-butynyl)benzoate (Taylor et al. J. Org. Chem., 1990, 55, 3222-3227) and 0.26 g (8% wt equivalent) of 10% palladium-on-carbon catalyst in 40 mL of ethanol. Hydrogenation was carried out at 50 psi of hydrogen for 18 hours. The mixture was filtered through a silica gel pad that was subsequently washed with ethanol. The combined filtrates were concentrated under reduced pressure to give 3.20 g (97%) of methyl 4-(4-hydroxybutyl)benzoate as a light yellow oil. 1H NMR (CDCl3) δ 1.51 (1H, s), 1.57-1.82 (4H, m), 2.74 (2H, t, J=7.3 Hz), 3.71 (2H, t, J=6.0 Hz), 3.94 (3H, s), 7.27 (2H, d, J=8.0 Hz), 7.99 (2H, d, J=8.0 Hz). The mixture was filtered through a silica gel pad that was subsequently washed with ethanol The combined filtrates were concentrated under reduced pressure

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

Procedure: To mixture of 4.19 g (1.5 eq) of pyridinium chlorochromate and 1.76 g (1.0 eq) of sodium acetate in 100 mL of dry methylene chloride are added, under nitrogen and with stirring, 2.70 g 1.0 eq) of methyl 4-(4-hydroxybutyl)benzoate in 50 mL of dry methylene chloride. The reaction mixture is stirred 12 hours, diluted with diethyl ether, and filtered. After concentration at reduced pressure, the residue is distilled under vacuum to yield 4-(4-carbomethoxyphenyl)-butanal as an oil, b.p. 131° C. at <1 torr; IR (film) νmax 2950, 2720, 1722, 1612, 1285, and 1110 cm-1 ; 1H NMR (CDCl3) delta 9.77 (m, 1H, --CHO), 7.98 (d, J=9 Hz, 2H, Ar), 7.24 (d, J=8.2 Hz, 2H, Ar), 3.90 (s, 3H, --CH3), 2.72 (t, 2H, benzyl), 2.47 (mm, 2H, --CH2CHO), 1.95 (m, 2H, --CH2). are added, under nitrogen The reaction mixture is stirred 12 hours filtered After concentration at reduced pressure the residue is distilled under vacuum

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

Procedure: To mixture of 4.19 g (1.5 eq) of pyridinium chlorochromate and 1.76 g (1.0 eq) of sodium acetate in 100 mL of dry methylene chloride are added, under nitrogen and with stirring, 2.70 g 1.0 eq) of methyl 4-(4-hydroxybutyl)benzoate in 50 mL of dry methylene chloride. The reaction mixture is stirred 12 hours, diluted with diethyl ether, and filtered. After concentration at reduced pressure, the residue is distilled under vacuum to yield 4-(4-carbomethoxyphenyl)-butanal as an oil, b.p. 131° C. at <1 torr; IR (film) νmax 2950, 2720, 1722, 1612, 1285, and 1110 cm-1 ; 1H NMR (CDCl3) delta 9.77 (m, 1H, --CHO), 7.98 (d, J=9 Hz, 2H, Ar), 7.24 (d, J=8.2 Hz, 2H, Ar), 3.90 (s, 3H, --CH3), 2.72 (t, 2H, benzyl), 2.47 (mm, 2H, --CH2CHO), 1.95 (m, 2H, --CH2). are added, under nitrogen The reaction mixture is stirred 12 hours filtered After concentration at reduced pressure the residue is distilled under vacuum

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

Procedure: A mixture of 2.55 g of methyl 4-(4-hydrox-but-1-yn-1-yl)benzoate in 200 mL of ethanol is hydrogenated at 50 psi of hydrogen for 12 hours in the presence of 0.26 g (10% weight equivalent) of 5% palladium on charcoal. The reaction mixture is filtered through a silica gel pad, which is washed with ethanol, and concentrated to yield methyl 4-(4-hydroxybutyl)benzoate as an oil. IR (film) νmax 3390, 2965, 2920, 2850, 1705, 1605, 1568, 1520, 1500, 1410, 1387, 1362, 1308, 1286, 1250, 1160, 1055, 1013, 843, 755, and 695 cm-1 ; 1H NMR (CDCl3) delta 7.95 (d, J=8.1 Hz, 2H, Ar), 7.25 (d, J=8.1 Hz, 2H, Ar), 3.89 (s, 3H, --CH3), 3.65 (t, J=6.3 Hz, 2H, --CH2OH), 2.69 (t, J=7.5 Hz, 2H, benzyl), 1.66 (m, 4H, 2° aliphatic). The reaction mixture is filtered through a silica gel pad, which is washed with ethanol concentrated