1-phenylbutane-1,4-diol

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

Procedure: A solution of 35.6 g (0.20 mole) of benzoylpropionic acid in 100 ml of tetrahydrofuran was added dropwise to 300 ml of a 1 molar solution of borane tetrahydrofuran complex in tetrahydrofuran. The mixture was stirred at ambient temperatures for 60 hr, giving a gel. This was treated with 100 ml of 2N hydrochloric acid solution and the mixture stirred for 15 min. Most of the tetrahydrofuran was removed on a rotary evaporator and the residue partitioned between methylene chloride and water. The aqueous layer was extracted again with methylene chloride. The combined extract was washed with water, dried (sodium sulfate), and concentrated to yield 24.30 g of 1-phenyl-1,4-butanediol. This intermediate was dissolved in acetone and heated at reflux temperature for 5 hr while 30 g of manganese dioxide was added in five portions. The reaction mixture was filtered and concentrated to a brown oil that was chromatographed on silica gel using 15% ethyl acetate-85% methylene chloride to elute the fraction identified by 1H nmr as the title compound. The fraction weighed 11.20 g, after concentration and was shown to have a purity greater than 90%. giving a gel the mixture stirred for 15 min Most of the tetrahydrofuran was removed on a rotary evaporator the residue partitioned between methylene chloride and water The aqueous layer was extracted again with methylene chloride The combined extract was washed with water dried (sodium sulfate) concentrated

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

Procedure: 3-Benzoylpropionic acid 11a dissolved in THF was reacted with LiAlH4 according to the general procedure. The following workup procedure was used: H2O was added and THF was evaporated. Diethylether and HCl (2M) was added. The aqueous layer was extracted with diethylether and the combined organic layers were washed with H2O, aqueous NaHCO3 (saturated) and H2O. Drying (MgSO4), filtration and evaporation gave 80% yield of 6a. 1H-NMR: 7.35-7.22 (m, 5H, Ar--H); 4.70 (t, 1H, CH--OH); 3.64 (t, 2H, CH2OH); 3.10 (brs, 1H, CH--OH); 2.60 (brs, 1H, CH2 --OH); 1.84 (q, 2H, CH2 --CHOH); 1.72-1.61 (m, 2H, CH2CH2OH). THF was evaporated Diethylether and HCl (2M) was added The aqueous layer was extracted with diethylether the combined organic layers were washed with H2O, aqueous NaHCO3 (saturated) and H2O Drying (MgSO4), filtration and evaporation

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

Procedure: 3-Benzoylpropionic acid 11a dissolved in THF was reacted with LiAlH4 according to the general procedure. The following workup procedure was used: H2O was added and THF was evaporated. Diethylether and HCl (2M) was added. The aqueous layer was extracted with diethylether and the combined organic layers were washed with H2O, aqueous NaHCO3 (saturated) and H2O. Drying (MgSO4), filtration and evaporation gave 80% yield of 6a. 1H-NMR: 7.35-7.22 (m, 5H, Ar--H); 4.70 (t, 1H, CH--OH); 3.64 (t, 2H, CH2OH); 3.10 (brs, 1H, CH--OH); 2.60 (brs, 1H, CH2 --OH); 1.84 (q, 2H, CH2 --CHOH); 1.72-1.61 (m, 2H, CH2CH2OH). THF was evaporated Diethylether and HCl (2M) was added The aqueous layer was extracted with diethylether the combined organic layers were washed with H2O, aqueous NaHCO3 (saturated) and H2O Drying (MgSO4), filtration and evaporation

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

Procedure: A solution of 35.6 g (0.20 mole) of benzoylpropionic acid in 100 ml of tetrahydrofuran was added dropwise to 300 ml of a 1 molar solution of borane tetrahydrofuran complex in tetrahydrofuran. The mixture was stirred at ambient temperatures for 60 hr, giving a gel. This was treated with 100 ml of 2N hydrochloric acid solution and the mixture stirred for 15 min. Most of the tetrahydrofuran was removed on a rotary evaporator and the residue partitioned between methylene chloride and water. The aqueous layer was extracted again with methylene chloride. The combined extract was washed with water, dried (sodium sulfate), and concentrated to yield 24.30 g of 1-phenyl-1,4-butanediol. This intermediate was dissolved in acetone and heated at reflux temperature for 5 hr while 30 g of manganese dioxide was added in five portions. The reaction mixture was filtered and concentrated to a brown oil that was chromatographed on silica gel using 15% ethyl acetate-85% methylene chloride to elute the fraction identified by 1H nmr as the title compound. The fraction weighed 11.20 g, after concentration and was shown to have a purity greater than 90%. giving a gel the mixture stirred for 15 min Most of the tetrahydrofuran was removed on a rotary evaporator the residue partitioned between methylene chloride and water The aqueous layer was extracted again with methylene chloride The combined extract was washed with water dried (sodium sulfate) concentrated

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

Procedure: A solution of 35.6 g (0.20 mole) of benzoylpropionic acid in 100 ml of tetrahydrofuran was added dropwise to 300 ml of a 1 molar solution of borane tetrahydrofuran complex in tetrahydrofuran. The mixture was stirred at ambient temperatures for 60 hr, giving a gel. This was treated with 100 ml of 2N hydrochloric acid solution and the mixture stirred for 15 min. Most of the tetrahydrofuran was removed on a rotary evaporator and the residue partitioned between methylene chloride and water. The aqueous layer was extracted again with methylene chloride. The combined extract was washed with water, dried (sodium sulfate), and concentrated to yield 24.30 g of 1-phenyl-1,4-butanediol. This intermediate was dissolved in acetone and heated at reflux temperature for 5 hr while 30 g of manganese dioxide was added in five portions. The reaction mixture was filtered and concentrated to a brown oil that was chromatographed on silica gel using 15% ethyl acetate-85% methylene chloride to elute the fraction identified by 1H nmr as the title compound. The fraction weighed 11.20 g, after concentration and was shown to have a purity greater than 90%. giving a gel the mixture stirred for 15 min Most of the tetrahydrofuran was removed on a rotary evaporator the residue partitioned between methylene chloride and water The aqueous layer was extracted again with methylene chloride The combined extract was washed with water dried (sodium sulfate) concentrated

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

Procedure: 3-Benzoylpropionic acid 11a dissolved in THF was reacted with LiAlH4 according to the general procedure. The following workup procedure was used: H2O was added and THF was evaporated. Diethylether and HCl (2M) was added. The aqueous layer was extracted with diethylether and the combined organic layers were washed with H2O, aqueous NaHCO3 (saturated) and H2O. Drying (MgSO4), filtration and evaporation gave 80% yield of 6a. 1H-NMR: 7.35-7.22 (m, 5H, Ar--H); 4.70 (t, 1H, CH--OH); 3.64 (t, 2H, CH2OH); 3.10 (brs, 1H, CH--OH); 2.60 (brs, 1H, CH2 --OH); 1.84 (q, 2H, CH2 --CHOH); 1.72-1.61 (m, 2H, CH2CH2OH). THF was evaporated Diethylether and HCl (2M) was added The aqueous layer was extracted with diethylether the combined organic layers were washed with H2O, aqueous NaHCO3 (saturated) and H2O Drying (MgSO4), filtration and evaporation

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

Procedure: A solution of 35.6 g (0.20 mole) of benzoylpropionic acid in 100 ml of tetrahydrofuran was added dropwise to 300 ml of a 1 molar solution of borane tetrahydrofuran complex in tetrahydrofuran. The mixture was stirred at ambient temperatures for 60 hr, giving a gel. This was treated with 100 ml of 2N hydrochloric acid solution and the mixture stirred for 15 min. Most of the tetrahydrofuran was removed on a rotary evaporator and the residue partitioned between methylene chloride and water. The aqueous layer was extracted again with methylene chloride. The combined extract was washed with water, dried (sodium sulfate), and concentrated to yield 24.30 g of 1-phenyl-1,4-butanediol. This intermediate was dissolved in acetone and heated at reflux temperature for 5 hr while 30 g of manganese dioxide was added in five portions. The reaction mixture was filtered and concentrated to a brown oil that was chromatographed on silica gel using 15% ethyl acetate-85% methylene chloride to elute the fraction identified by 1H nmr as the title compound. The fraction weighed 11.20 g, after concentration and was shown to have a purity greater than 90%. giving a gel the mixture stirred for 15 min Most of the tetrahydrofuran was removed on a rotary evaporator the residue partitioned between methylene chloride and water The aqueous layer was extracted again with methylene chloride The combined extract was washed with water dried (sodium sulfate) concentrated

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

Procedure: A solution of 35.6 g (0.20 mole) of benzoylpropionic acid in 100 ml of tetrahydrofuran was added dropwise to 300 ml of a 1 molar solution of borane tetrahydrofuran complex in tetrahydrofuran. The mixture was stirred at ambient temperatures for 60 hr, giving a gel. This was treated with 100 ml of 2N hydrochloric acid solution and the mixture stirred for 15 min. Most of the tetrahydrofuran was removed on a rotary evaporator and the residue partitioned between methylene chloride and water. The aqueous layer was extracted again with methylene chloride. The combined extract was washed with water, dried (sodium sulfate), and concentrated to yield 24.30 g of 1-phenyl-1,4-butanediol. This intermediate was dissolved in acetone and heated at reflux temperature for 5 hr while 30 g of manganese dioxide was added in five portions. The reaction mixture was filtered and concentrated to a brown oil that was chromatographed on silica gel using 15% ethyl acetate-85% methylene chloride to elute the fraction identified by 1H nmr as the title compound. The fraction weighed 11.20 g, after concentration and was shown to have a purity greater than 90%. giving a gel the mixture stirred for 15 min Most of the tetrahydrofuran was removed on a rotary evaporator the residue partitioned between methylene chloride and water The aqueous layer was extracted again with methylene chloride The combined extract was washed with water dried (sodium sulfate) concentrated

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

Procedure: 1-Naphthyl isocyanate (4.3 ml, 30 mmol) in 50 ml of methylene chloride was added under nitrogen dropwise over 1 hour to a solution of 4-phenyl-4-hydroxybutanol (5.00 g, 30 mmol), prepared in step (a) of Example 6, and triethylamine (4.2 ml, 30 mmol) in 200 ml of methylene chloride at room temperature. After the addition the reaction was stirred at room temperature for 18 hours. The solid present in the reaction was removed by filtration. The filtrate was extracted with 1 N HCl, dried (MgSO4) and the solvent removed under reduced pressure to give 10.08 g of a clear oil Purification of the oil by chromatography on 1 kg of silica gel (230-400 mesh) using 3%-20% ethyl acetate-methylene chloride as the eluent gave naphthalen-1-yl-carbamic acid 4-hydroxy-4-phenyl-butyl ester (7.73 g, 77%) as a white solid, mp 92-92° C. After the addition the reaction The solid present in the reaction was removed by filtration The filtrate was extracted with 1 N HCl dried (MgSO4) the solvent removed under reduced pressure to give 10.08 g of a clear oil Purification of the oil by chromatography on 1 kg of silica gel (230-400 mesh)

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

Procedure: Methyl 3-benzoylpropionate (50 g, 0.25 mol) in 300 ml of anhydrous THF was added under nitrogen dropwise over one hour to a suspension of LAH in 500 ml of anhydrous THF. After the addition the mixture was refluxed for 20 hours. After cooling to room temperature 14.3 ml of water was added dropwise followed by the addition of 14.3 ml of 15% KOH and then 42.9 ml of water. The mixture was stirred for 30 minutes and then filtered. The filtrate was concentrated under reduced pressure to remove the THF. The residue was partitioned between methylene chloride and 1 N HCl. The organic layer was separated and the aqueous layer extracted three times with methylene chloride. The organic extracts were combined, dried (MgSO4) and the solvent removed under reduced pressure to give 4-phenyl-4-hydroxybutanol (37.90 g, 91%) as a white solid, mp 63-68° C. After the addition the mixture was refluxed for 20 hours was added dropwise filtered The filtrate was concentrated under reduced pressure to remove the THF The residue was partitioned between methylene chloride and 1 N HCl The organic layer was separated the aqueous layer extracted three times with methylene chloride dried (MgSO4) the solvent removed under reduced pressure

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

Procedure: A solution of 35.6 g (0.20 mole) of benzoylpropionic acid in 100 ml of tetrahydrofuran was added dropwise to 300 ml of a 1 molar solution of borane tetrahydrofuran complex in tetrahydrofuran. The mixture was stirred at ambient temperatures for 60 hr, giving a gel. This was treated with 100 ml of 2N hydrochloric acid solution and the mixture stirred for 15 min. Most of the tetrahydrofuran was removed on a rotary evaporator and the residue partitioned between methylene chloride and water. The aqueous layer was extracted again with methylene chloride. The combined extract was washed with water, dried (sodium sulfate), and concentrated to yield 24.30 g of 1-phenyl-1,4-butanediol. This intermediate was dissolved in acetone and heated at reflux temperature for 5 hr while 30 g of manganese dioxide was added in five portions. The reaction mixture was filtered and concentrated to a brown oil that was chromatographed on silica gel using 15% ethyl acetate-85% methylene chloride to elute the fraction identified by 1H nmr as the title compound. The fraction weighed 11.20 g, after concentration and was shown to have a purity greater than 90%. giving a gel the mixture stirred for 15 min Most of the tetrahydrofuran was removed on a rotary evaporator the residue partitioned between methylene chloride and water The aqueous layer was extracted again with methylene chloride The combined extract was washed with water dried (sodium sulfate) concentrated

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

Procedure: 3-Benzoylpropionic acid 11a dissolved in THF was reacted with LiAlH4 according to the general procedure. The following workup procedure was used: H2O was added and THF was evaporated. Diethylether and HCl (2M) was added. The aqueous layer was extracted with diethylether and the combined organic layers were washed with H2O, aqueous NaHCO3 (saturated) and H2O. Drying (MgSO4), filtration and evaporation gave 80% yield of 6a. 1H-NMR: 7.35-7.22 (m, 5H, Ar--H); 4.70 (t, 1H, CH--OH); 3.64 (t, 2H, CH2OH); 3.10 (brs, 1H, CH--OH); 2.60 (brs, 1H, CH2 --OH); 1.84 (q, 2H, CH2 --CHOH); 1.72-1.61 (m, 2H, CH2CH2OH). THF was evaporated Diethylether and HCl (2M) was added The aqueous layer was extracted with diethylether the combined organic layers were washed with H2O, aqueous NaHCO3 (saturated) and H2O Drying (MgSO4), filtration and evaporation