1,5-diphenylpentan-3-one

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

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

Procedure: A solution of 1,5-di-(phenyl)-3-pentanone (9.5 g., 0.04 mole) in 50 cc. of anhydrous ethanol is added dropwise over about 20 minutes to a stirred solution of 1,3-diamino-2-hydroxypropane (25 g., 0.27 mole) in 200 cc. of ethanol. The resulting mixture is then heated at reflux for about two hours, allowed to cool, 1.0 g. platinum oxide added, and the mixture reduced under a 40 psi hydrogen atmosphere until hydrogen uptake ceases. The mixture is then filtered from the catalyst, concentrated in vacuo to remove the ethanol, the residue taken up in ether (250 cc.), washed with water, dried over sodium sulfate, filtered and concentrated in vacuo to yield the product 1-amino-3-[1,5-di-(phenyl)-3-pentylamino]-2-propanol. The resulting mixture is then heated at reflux for about two hours to cool The mixture is then filtered from the catalyst concentrated in vacuo to remove the ethanol washed with water dried over sodium sulfate filtered concentrated in vacuo

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

Procedure: To a solution of 1,5-Diphenylpentan-3-one (5.26 g, 22.1 mmol), ammonium acetate (8.52 g, 110.5 mmol) and sodium acetate (9.06 g, 110.5 mmol) in methanol (80 mL) was added a solution of sodium cyanoborohydride (1.67 g, 26.52 mmol) in methanol (20 mL) and the reaction heated to reflux. After stirring at reflux for 30 min, the reaction was cooled and concentrated to dryness. The residue was partioned between methylene chloride and 2N sodium hydroxide. The organic phase was separated, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Chromatography of the residue on silica gel (elution with 2-5% methanol/methylene chloride) provided N-(1-phenethyl-3-phenyl-propyl)amine. To a solution of the above amine (2.1 g, 8.82 mmol) in ethanol (50 mL), was added 2-imidazole-carboxaldehyde (813 mg, 8.47 mmol) and the reaction heated to 50° C. After stirring for 2 hr, the resulting homogeneous solution was treated with sodium borohydride (400 mg, 10.58 mmol) and allowed to stir overnight. The reaction was concentrated to dryness and the residue was partioned between methylene chloride and 2N sodium hydroxide. The organic phase was separated, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Chromatography of the residue on silica gel (elution with 5% methanol/methylene chloride) provided compound 22. the reaction heated to reflux at reflux for 30 min the reaction was cooled concentrated to dryness The organic phase was separated washed with brine dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: Freshly distilled THF (25 mL) was cooled in an ice bath under a nitrogen atmosphere, then charged with 660 mg (16.5 mmol) sodium hydride (60% dispersion). This suspension was treated with 1.89 g (16.3 mmol) methyl acetoacetate dropwise, and the reaction was stirred for 10 minutes. n-Butyllithium (10.3 mL of 1.6M in hexanes; 16.5 mmol) was dripped in and the reaction was stirred 30 minutes. At this time 3.10 g (13 mmol) of 1,5-diphenyl-3-pentanone (Ram and Spicer, Tetrahedrom Lett., 1988, 29 (31), 3741) in 20 mL THF was added dropwise over 15 minutes. After 4 hours 100 mL H2O was added and the reaction stirred overnight. The reaction was extracted with diethyl ether, and the organics set aside. The aqueous layer was chilled, treated with 50% HOAc until a precipitate formed, and then extracted with EtOAc. These organics were washed with saturated brine, dried (Na2SO4), and concentrated. 1H NMR (DMSO-d6) δ 2.0 (d of d, 4 H), 2.65 (m, 6 H), 5.0 (s, 1 H), 7.15-7.35 (m, 10 H), 11.4 (bs, 1 H). was stirred 30 minutes the reaction stirred overnight The reaction was extracted with diethyl ether The aqueous layer was chilled treated with 50% HOAc until a precipitate formed extracted with EtOAc These organics were washed with saturated brine dried (Na2SO4) concentrated

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

Procedure: A solution of 135 mg (0.6 mmol) of 1,5-diphenyl-3-pentanone, 0.2 ml of ethylene glycol, and 10 mg of p-toluene sulfonic acid monohydrate was refluxed with azeotropic removal of water. After separation of water was completed, the solution was diluted with ethyl acetate, washed sequentially with aqueous NaHCO and water, dried over Na2SO4, and concentrated to provide the desired compound. 1H NMR (CDCl3) δ2.0 (m, 4H), 2.71 (m, 4H), 4.03 (s, 4H), 7.15-7.3 (m, 10H). Mass spectrum: (M+H)+ =283. After separation of water the solution was diluted with ethyl acetate washed sequentially with aqueous NaHCO and water dried over Na2SO4 concentrated

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

Procedure: A solution of 0.37 g (1.55 mmol) of 1,5-diphenyl-3-pentanone in 20 ml of 2-propanol was treated with 0.22 g (3.1 mmol) of hydroxylamine hydrochloride and 0.31 g (4.7 mmol) of anhydrous sodium acetate. After being stirred for 10 min, the mixture was treated with 0.20 g (3.2 mmol) of sodium cyanoborohydride and stirred at ambient temperature for 16 h. After concentration in vacuo, the residue was taken up in ethyl acetate, washed sequentially with aqueous NaHCO3 and saturated brine, dried over MgSO4, and concentrated. Flash chromatography using 40% ethyl acetate in chloroform gave 121 mg (31%) of the desired compound (Rf 0.16, 30% ethyl acetate in chloroform) as a white solid, m.p. 54°-55° C. 1H NMR (CDCl3) δ1.7-1.85 (m, 2H), 1.85-2.0 (m, 2H), 2.6-2.75 (m, 4H), 2.90 (pentet, J=6 Hz, 1H), 5.22 (br, 2H), 7.1-7.35 (m, 10H). Mass spectrum (M+H)+ =256. stirred at ambient temperature for 16 h After concentration in vacuo washed sequentially with aqueous NaHCO3 and saturated brine dried over MgSO4 concentrated

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

Procedure: A mixture of 1.00 g (4.27 mmol) of dibenzylidene acetone and 0.15 g of 10% palladium on carbon in 150 ml of methyl cellusolve was shaken under 4 atm. of hydrogen for 2 h. The solution was filtered and concentrated in vacuo. Flash chromatography using 10-20% ethyl acetate in hexane gave 0.60 g (59%) of 1,5-diphenyl-3-pentanone (Rf 0.43, 20% ethyl acetate in hexane) as a colorless oil and 0.29 g (28%) of 1,5-diphenyl-3-pentanol (Rf 0.36) as a white solid, m.p. 43°-45° C. 1,5-Diphenyl-3-pentanone: 1H NMR (CDCl3) δ2.71 (t, J=7 Hz, 4H), 2.89 (t, J=7 Hz, 4H), 7.1-7.3 (m, 10H). Mass spectrum (M+NH4)+ =256. The solution was filtered concentrated in vacuo

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

Procedure: To a solution of 1,5-Diphenylpentan-3-one (5.26 g, 22.1 mmol), ammonium acetate (8.52 g, 110.5 mmol) and sodium acetate (9.06 g, 110.5 mmol) in methanol (80 mL) was added a solution of sodium cyanoborohydride (1.67 g, 26.52 mmol) in methanol (20 mL) and the reaction heated to reflux. After stirring at reflux for 30 min, the reaction was cooled and concentrated to dryness. The residue was partioned between methylene chloride and 2N sodium hydroxide. The organic phase was separated, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Chromatography of the residue on silica gel (elution with 2-5% methanol/methylene chloride) provided N-(1-phenethyl-3-phenyl-propyl)amine. To a solution of the above amine (2.1 g, 8.82 mmol) in ethanol (50 mL), was added 2-imidazole-carboxaldehyde (813 mg, 8.47 mmol) and the reaction heated to 50° C. After stirring for 2 hr, the resulting homogeneous solution was treated with sodium borohydride (400 mg, 10.58 mmol) and allowed to stir overnight. The reaction was concentrated to dryness and the residue was partioned between methylene chloride and 2N sodium hydroxide. The organic phase was separated, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Chromatography of the residue on silica gel (elution with 5% methanol/methylene chloride) provided compound 22. the reaction heated to reflux at reflux for 30 min the reaction was cooled concentrated to dryness The organic phase was separated washed with brine dried over anhydrous magnesium sulfate filtered concentrated in vacuo

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

Procedure: Freshly distilled THF (25 mL) was cooled in an ice bath under a nitrogen atmosphere, then charged with 660 mg (16.5 mmol) sodium hydride (60% dispersion). This suspension was treated with 1.89 g (16.3 mmol) methyl acetoacetate dropwise, and the reaction was stirred for 10 minutes. n-Butyllithium (10.3 mL of 1.6 M in hexanes; 16.5 mmol) was dripped in and the reaction was stirred 30 minutes. At this time 3.10 g (13 mmol) of 1,5-diphenyl-3-pentanone (Ram and Spicer, Tetrahedrom Lett., 1988, 29 (31), 3741) in 20 mL THF was added dropwise over 15 minutes. After 4 hours 100 mL H2O was added and the reaction stirred overnight. The reaction was extracted with diethyl ether, and the organics set aside. The aqueous layer was chilled, treated with 50% HOAc until a precipitate formed, and then extracted with EtOAc. These organics were washed with saturated brine, dried (Na2SO4), and concentrated. 1H NMR (DMSO-d6) δ 2.0 (d of d, 4 H), 2.65 (m, 6 H), 5.0 (s, 1 H), 7.15-7.35 (m, 10 H), 11.4 (bs, 1 H). was stirred 30 minutes the reaction stirred overnight The reaction was extracted with diethyl ether The aqueous layer was chilled treated with 50% HOAc until a precipitate formed extracted with EtOAc These organics were washed with saturated brine dried (Na2SO4) concentrated

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

Procedure: A solution of 0.37 g (1.55 mmol) of 1,5-diphenyl-3-pentanone in 20 ml of 2-propanol was treated with 0.22g (3.1 mmol) of hydroxylamine hydrochloride and 0.31 g (4.7 mmol) of anhydrous sodium acetate. After being stirred for 10 min, the mixture was treated with 0.20 g (3.2 mmol) of sodium cyanoborohydride and stirred at ambient temperature for 16 h. After concentration in vacuo, the residue was taken up in ethyl acetate, washed sequentially with aqueous NaHCO3 and saturated brine, dried over MgSO4, and concentrated. Flash chromatography using 40% ethyl acetate in chloroform gave 121 mg (31%) of the desired compound (Rf 0.16, 30% ethyl acetate in chloroform) as a white solid, m.p. 54°-55° C. 1H NMR (CDCl3) δ 1.7-1.85 (m, 2H), 1.85-2.0 (m, 2H), 2.6-2.75 (m, 4H), 2.90 (pentet, J=6 Hz, 1H), 5.22 (br, 2H), 7.1-7.35 (m, 10H). Mass spectrum (M+H)+ =256. stirred at ambient temperature for 16 h After concentration in vacuo washed sequentially with aqueous NaHCO3 and saturated brine dried over MgSO4 concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 1.59 g (4.45 mmol) of methyltriphenylphosphonium bromide in 100 ml of tetrahydrofuran was cooled to -78° C., treated with 2.2 ml (4.5 mmol) of n-butyllithium, warmed to 0° C, was recooled to -78° C. The resulting solution was treated via cannula with a solution of 1.59 g (4.45 mmol) of 1,5diphenyl-3-pentanone in 20 ml of tetrahydrofuran. After being allowed to stir at ambient temperature for 2 h, the solution was diluted with hexane, washed sequentially with water and saturated brine, dried over MgSO4, and concentrated in vacuo. The mixture was purified by flash chromatography to give 0.90 g (86%) of the desired compound as a colorless oil. 1H NMR (CDCl3) δ 2.37 (t, J=8 Hz, 4H), 2.76 (t, J=8 Hz, 4H), 4.81 (s, 2H), 7.15-7.3 (m, 10H). Mass spectrum (M+NH4)+ =254. warmed to 0° C was recooled to -78° C washed sequentially with water and saturated brine dried over MgSO4 concentrated in vacuo The mixture was purified by flash chromatography

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

Procedure: A mixture of 1.00 g (4.27 mmol) of dibenzylidene acetone and 0.15 g of 10% palladium on carbon in 150 ml of methyl cellusolve was shaken under 4 atm. of hydrogen for 2 h. The solution was filtered and concentrated in vacuo. Flash chromatography using 10-20% ethyl acetate in hexane gave 0.60 g (59%) of 1,5-diphenyl-3-pentanone (Rf 0.43, 20% ethyl acetate in hexane) as a colorless Oil and 0.29 g (28%) of 1,5-diphenyl-3-pentanol (Rf 0.36) as a white solid, m.p. 43°-5° C. 1,5-Diphenyl-3-pentanone: 1H NMR (CDCl3) δ 2.71 (t, J=7 Hz, 4H), 2.89 (t, J=7 Hz, 4H), 7.1-7.3 (m, 10H). Mass spectrum (M+NH4)+ 256. The solution was filtered concentrated in vacuo