4-(4-methoxyphenyl)butan-1-ol

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

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 4-(4-methoxyphenyl)butan-1-ol (9.37 g, 52 mmol, Aldrich) in dry toluene (185 mL) under an argon atmosphere was added triphenylphosphine (17.8 g, 67.6 mmol) and imidazole (10.6 g, 156 mmol). After ten minutes I2 (17.1 g, 67.6 mmol) was added. The reaction was then heated at 65 ° C. for 30 minutes. Upon cooling to room temperature the reaction was concentrated to 1/4 volume. The remaining solution was diluted with Et2O and washed with H2O and brine and dried (MgSO4). The solvent was removed and the resulting residue was dissolved in CH2Cl2 and applied to a flash chromatography column (silica). Elution with 2% EtOAc in hexane provided a colorless oil: 1H NMR (250 MHz, CDCl3) δ7.08 (d, J=8.7 Hz, 2H, phenyl), 6.82 (d, J=8.7 Hz, 2H, phenyl), 3.78 (s, 3H, OMe), 3.17 (t, J=7.4 Hz, 2H, I-CH2), 2.54 (t, J=7.2 Hz, 2H, benzylic), 1.85 (m, 2H, CH2), 160 (m, 2H, CH2). Upon cooling to room temperature the reaction was concentrated to 1/4 volume The remaining solution was diluted with Et2O washed with H2O and brine dried (MgSO4) The solvent was removed the resulting residue was dissolved in CH2Cl2 Elution with 2% EtOAc in hexane provided a colorless oil

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 4-(4-methoxyphenyl)butan-1-ol (9.37 g, 52 mmol, Aldrich) in dry toluene (185 mL) under an argon atmosphere was added triphenylphosphine (17.8 g, 67.6 mmol) and imidazole (10.6 g, 156 mmol). After ten minutes I2 (17.1 g, 67.6 mmol) was added. The reaction was then heated at 65 ° C. for 30 minutes. Upon cooling to room temperature the reaction was concentrated to 1/4 volume. The remaining solution was diluted with Et2O and washed with H2O and brine and dried (MgSO4). The solvent was removed and the resulting residue was dissolved in CH2Cl2 and applied to a flash chromatography column (silica). Elution with 2% EtOAc in hexane provided a colorless oil: 1H NMR (250 MHz, CDCl3) δ7.08 (d, J=8.7 Hz, 2H, phenyl), 6.82 (d, J=8.7 Hz, 2H, phenyl), 3.78 (s, 3H, OMe), 3.17 (t, J=7.4 Hz, 2H, I-CH2), 2.54 (t, J=7.2 Hz, 2H, benzylic), 1.85 (m, 2H, CH2), 160 (m, 2H, CH2). Upon cooling to room temperature the reaction was concentrated to 1/4 volume The remaining solution was diluted with Et2O washed with H2O and brine dried (MgSO4) The solvent was removed the resulting residue was dissolved in CH2Cl2 Elution with 2% EtOAc in hexane provided a colorless oil

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(4-methoxyphenyl)butanol (100 g, 0.55 mole) in dichloromethane, cooled to -75° C. in a dry ice-acetone bath, a solution of boron tribromide (278 g; 2.0 mole) was added slowly over one hour. The cooling bath was then removed and the reaction mixture allowed to warm to 15° C. slowly. The reaction was shown to be complete by thin layer chromatography (TLC). The reaction mixture was again cooled in an ice-water bath; 10% sodium hydroxide solution was added until pH of about 9 was obtained. The resulting mixture was then acidified with concentrated HCl to a pH of about 2. The organic layer was separated, the aqueous layer was extracted once with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give 90 g of crude product. The crude product was purified by dry filtration chromatography using 10% ethyl acetate/dichloromethane as eluent giving an 86% yield of pure 4-(4-hydroxyphenyl)butanol. The 1H NMR was consistent with the assigned structure. The cooling bath was then removed The reaction mixture was again cooled in an ice-water bath 10% sodium hydroxide solution was added until pH of about 9 was obtained The organic layer was separated the aqueous layer was extracted once with ethyl acetate The combined organic layers were dried over magnesium sulfate filtered concentrated to give 90 g of crude product The crude product was purified by dry filtration chromatography

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

Procedure: (3.3 g), b.p. 180°-190°/0.5 torr, from 1,6-dibromohexane (8 g) and 4-(4-methoxyphenyl)butanol (2 g).

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

Procedure: (3.3 g), b.p. 180°-190°/0.5 torr, from 1,6-dibromohexane (8 g) and 4-(4-methoxyphenyl)butanol (2 g).

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

Procedure: To a stirred solution of 4-(4-methoxyphenyl)butanol (1 equiv.) in dry dichloromethane at −10° C. under an argon atmosphere was added boron tribromide (2.7 equiv., using a 1 M solution of boron tribromide in CH2Cl2). Stirring was continued at that temperature until completion of the reaction (4 hours). Unreacted boron tribromide was destroyed by addition of aqueous saturated NaHCO3 solution at 0° C. The resulting mixture diluted with CH2Cl2 and water, the organic phase was separated, washed with brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on silica gel (30% diethyl ether-hexane) afforded the title compound in 42% yield. was continued at that temperature until completion of the reaction (4 hours) was destroyed by addition of aqueous saturated NaHCO3 solution at 0° C The resulting mixture diluted with CH2Cl2 and water the organic phase was separated washed with brine dried (MgSO4) evaporated Purification by flash column chromatography on silica gel (30% diethyl ether-hexane)

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

Procedure: To a stirred solution of 4-(4-methoxyphenyl)butanol (1 equiv.) in dry dichloromethane at −10° C. under an argon atmosphere was added boron tribromide (2.7 equiv., using a 1 M solution of boron tribromide in CH2Cl2). Stirring was continued at that temperature until completion of the reaction (4 hours). Unreacted boron tribromide was destroyed by addition of aqueous saturated NaHCO3 solution at 0° C. The resulting mixture diluted with CH2Cl2 and water, the organic phase was separated, washed with brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on silica gel (30% diethyl ether-hexane) afforded the title compound in 42% yield. was continued at that temperature until completion of the reaction (4 hours) was destroyed by addition of aqueous saturated NaHCO3 solution at 0° C The resulting mixture diluted with CH2Cl2 and water the organic phase was separated washed with brine dried (MgSO4) evaporated Purification by flash column chromatography on silica gel (30% diethyl ether-hexane)

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

Procedure: Ammonia (75 ml) is liquified in a flask at -40° and a solution of 5 g (28 mmol) of p-(4-hydroxybutyl)-anisole in 25 ml ethanol is added 2.76 g (0.12 mmol) of sodium is added in small pieces over 1 h. The blue solution is then stirred at -40° for 10 min during which time the solution decolorizes with the formation of a white precipitate. The reaction is quenched using 5.88 g solid ammonium chloride followed by 25 ml water. The solvent is evaporated under a stream of nitrogen and then poured into brine and extracted with ether (4×100 ml). The organic extracts are combined, dried, filtered and subjected to evaporation to give 1-methoxy-4-(4-hydroxybutyl)-cyclohexa-1,4-diene as an oil. is added in small pieces over 1 h The reaction is quenched The solvent is evaporated under a stream of nitrogen poured into brine extracted with ether (4×100 ml) dried filtered subjected to evaporation

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

Procedure: Pyridine (15 mL) was added drop wise to a cooled (0 ° C.) solution of 4-(4-methoxyphenyl)butanol (10.0 g, 0.055 mol) and p-toluenesulfonyl chloride (13.6 g, 0.072 mol) in dry chloroform (100 mL) under stirring. The reaction mixture was stirred overnight at room temperature. After this time, the reaction was quenched with 10% HCl (300 mL) and extracted with chloroform. The organic fraction was washed with saturated NaHCO3, water and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by flash chromatography (eluent: hexane/ethyl acetate 15:1) to provide 12.9 g (66%) of 1 as clear oil. 1H NMR (360 MHz, CDCl3) δ 1.61 (m, 4H), 2.44 (s, 3H), 2.52 (m, 2H), 3.78 (s, 3H), 4.05 (m, 2H), 6.77 (d, 2H), 7.05 (d, 2H), 7.34 (d, 2H), 7.78 (d, 2H). The reaction mixture was stirred overnight at room temperature After this time, the reaction was quenched with 10% HCl (300 mL) extracted with chloroform The organic fraction was washed with saturated NaHCO3, water dried over magnesium sulfate The solvent was removed under reduced pressure the residue purified by flash chromatography (eluent: hexane/ethyl acetate 15:1)

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

Procedure: Pyridine (15 mL) was added drop wise to a cooled (0° C.) solution of 4-(4-methoxyphenyl)butanol (10.0 g, 0.055 mol) and p-toluenesulfonyl chloride (13.6 g, 0.072 mol) in dry chloroform (100 mL) under stirring. The reaction mixture was stirred overnight at room temperature. After this time, the reaction was quenched with 10% HCl (300 mL) and extracted with chloroform. The organic fraction was washed with saturated NaHCO3, water and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by flash chromatography (eluent:hexane/ethyl acetate 15:1) to provide 12.9 g (66%) of 1 as clear oil. 1H NMR (360 MHz, CDCl3) δ 1.61 (m, 4H), 2.44 (s, 3H), 2.52 (m, 2H), 3.78 (s, 3H), 4.05 (m, 2H), 6.77 (d, 2H), 7.05 (d, 2H), 7.34 (d, 2H), 7.78 (d, 2H). The reaction mixture was stirred overnight at room temperature After this time, the reaction was quenched with 10% HCl (300 mL) extracted with chloroform The organic fraction was washed with saturated NaHCO3, water dried over magnesium sulfate The solvent was removed under reduced pressure the residue purified by flash chromatography (eluent:hexane/ethyl acetate 15:1)

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

Procedure: Pyridine (15 mL) was added dropwise to a cooled (0° C.) solution of 4-(4-methoxyphenyl)butanol (10.0 g, 0.055 mol) and p-toluenesulfonyl chloride (13.6 g, 0.072 mol) in dry chloroform (100 mL) under stirring. The reaction mixture was stirred overnight at room temperature. After this time, the reaction was quenched with 10% HCl (300 mL) and extracted with chloroform. The organic fraction was washed with saturated NaHCO3, water and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by flash chromatography (eluent: hexane, ethyl acetate=15:1) to provide 12.9 g (66%) of I as clear oil. 1H NMR (360 MHZ, CDCl3) δ 1.61 (m, 4H), 2.44 (s, 3H), 2.52 (m, 2H), 3.78 (s, 3H), 4.05 (m, 2H), 6.77 (d, J=12.5 Hz, 2H), 7.05 (d, J=12.5 Hz, 2H), 7.34 (d, J=10.5 Hz, 2H), 7.78 (d, J=10.5 Hz, 2H). The reaction mixture was stirred overnight at room temperature After this time, the reaction was quenched with 10% HCl (300 mL) extracted with chloroform The organic fraction was washed with saturated NaHCO3, water dried over magnesium sulfate The solvent was removed under reduced pressure the residue purified by flash chromatography (eluent: hexane, ethyl acetate=15:1) to provide 12.9 g (66%) of I as clear oil