2-(2-phenylethyl)benzaldehyde

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

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

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (9.1 ml) was added to a suspension of 2-bibenzylcarboxylic acid (20 g) in dichloromethane (200 ml) followed by 0.1 ml of DMF. The mixture was stirred for 15 hours and evaporated to dryness. The residue was dissolved in diglyme (150 ml) and cooled to -70° C. under argon. Lithium tri-t-butoxyaluminohydride (177 ml of a 0.5M solution in diglyme) was added dropwise such that the temperature of the reaction mixture did not exceed -65° C. The reaction mixture was stirred for a further 2 hours at -70° C. and then poured onto ice. The slurry obtained was acidified (HCl) and extracted with diethyl ether (3×75 ml). The combined ether extracts were washed with brine and dried (MgSO4). The solvent was removed and the residue dissolved in petroleum ether (BP 60°-80° C.) and washed once with aqueous saturated sodium bicarbonate, five times with water and twice with brine then dried. Removal of the solvent gave an oil which was purified by chromatography on silica, eluting with dichloromethane-hexane (1:1 v/v), to give 2-(phenethyl)benzaldehyde, (4.83 g). evaporated to dryness The residue was dissolved in diglyme (150 ml) Lithium tri-t-butoxyaluminohydride (177 ml of a 0.5M solution in diglyme) was added dropwise such that the temperature of the reaction mixture did not exceed -65° C The reaction mixture was stirred for a further 2 hours at -70° C. poured onto ice The slurry obtained extracted with diethyl ether (3×75 ml) The combined ether extracts were washed with brine dried (MgSO4) The solvent was removed the residue dissolved in petroleum ether (BP 60°-80° C.) washed once with aqueous saturated sodium bicarbonate, five times with water and twice with brine then dried Removal of the solvent gave an oil which was purified by chromatography on silica eluting with dichloromethane-hexane (1:1 v/v)

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

Procedure: Methyl 4-[2-(phenethyl)phenethyl]benzoate was prepared from 2-phenethylbenzaldehyde and 4-carboxybenzyltriphenylphosphonium bromide using a similar method to the described in Example 24 for the preparation of methyl 4-[3-(2-(phenethyl)phenyl)propyl]benzoate.

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(phenethyl)benzoic acid (commercially available) (11.3 g), oxalyl chloride (5.2 ml), and DMF (2 drops) in dichloromethane (100 ml) was stirred for 1.5 hours. The resulting solution was evaporated and the residue dissolved in diglyme (75 ml) and cooled to -70° C. Li(OtBu)3H (100 ml of 0.5M solution in diglyme) was added dropwise over 45 minutes and the mixture stirred at -70° C. for 1 hour. The solution was poured into 2N aqueous hydrochloric acid and the mixture extracted with iso-hexane (3×100 ml). The combined extracts were washed with saturated aqueous sodium hydrogen carbonate, water and brine and dried (MgSO4). The solvent was evaporated and the residue purified by medium pressure chromatography on silica gel eluting with a mixture of dichloromethane and iso-hexane (1:1) to give 2-(phenethyl)benzaldehyde acid as a colourless oil (7.77 g). The resulting solution was evaporated the residue dissolved in diglyme (75 ml) Li(OtBu)3H (100 ml of 0.5M solution in diglyme) was added dropwise over 45 minutes the mixture stirred at -70° C. for 1 hour The solution was poured into 2N aqueous hydrochloric acid the mixture extracted with iso-hexane (3×100 ml) The combined extracts were washed with saturated aqueous sodium hydrogen carbonate, water and brine dried (MgSO4) The solvent was evaporated the residue purified by medium pressure chromatography on silica gel eluting with a mixture of dichloromethane and iso-hexane (1:1)

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

Procedure: Methyl 4-[N-(2-(phenethyl)benzyl)amino]benzoate was prepared from 2-(phenethyl)benzaldehyde and methyl 4-aminobenzoate using a similar method to that of Example 4 paragraph (G).

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-phenethyl benzoic acid (11.3 g), oxalyl chloride (5.2 ml), DMF (0.2 ml) and dichloromethane (100 ml) was stirred for 1.5 hours. The solvent was evaporated, diglyme (75 ml) added and the mixture cooled to -70° C. Lithium tri-(tert-butoxy)aluminium hydride (100 ml, 0.5M solution in diglyme) was added dropwise over 45 minutes maintaining the reaction temperature below -60° C. The reaction was stirred at -70° C. for 1 hour and poured into a 2N HCl and ice mixture. The mixture was extracted with iso-hexane (3×100 ml). The extracts were washed with saturated aqueous sodium hydrogen carbonate, water and brine, dried (MgSO4), filtered and evaporated. The residue was purfied by MPLC eluting with dichloromethane/iso-hexane (1:1) to give 2-(phenethyl)benzaldehyde (7.77 g). The solvent was evaporated diglyme (75 ml) added Lithium tri-(tert-butoxy)aluminium hydride (100 ml, 0.5M solution in diglyme) was added dropwise over 45 minutes maintaining the reaction temperature below -60° C The reaction was stirred at -70° C. for 1 hour poured into a 2N HCl and ice mixture The mixture was extracted with iso-hexane (3×100 ml) The extracts were washed with saturated aqueous sodium hydrogen carbonate, water and brine dried (MgSO4) filtered evaporated eluting with dichloromethane/iso-hexane (1:1)

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

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

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (9.1 ml) was added to a suspension of 2-bibenzylcarboxylic acid (2-phenethylbenzoic acid) (20 g) in dichloromethane (200 ml) followed by 0.1 ml of DMF. The mixture was stirred for 15 hours and evaporated to dryness. The residue was dissolved in diglyme (150 ml) and cooled to -70° C. under argon. Lithium tri-t-butoxyaluminohydride (177 ml of a 0.5M solution in diglyme) was added dropwise such that the temperature of the reaction mixture did not exceed -65° C. The reaction mixture was stirred for a further 2 hours at -70° C. and then poured onto ice. The slurry obtained was acidified (HCl) and extracted with diethyl ether (3×75 ml). The combined ether extracts were washed with brine and dried (MgSO4). The solvent was removed and the residue dissolved in petroleum ether (BP 60-80° C.) and washed once with aqueous saturated sodium bicarbonate, five times with water and twice with brine then dried. Removal of the solvent gave an oil which was purified by chromatography on silica, eluting with dichloromethane-hexane (1:1 v/v), to give 2-(phenethyl)benzaldehyde. (4.83 g). evaporated to dryness The residue was dissolved in diglyme (150 ml) Lithium tri-t-butoxyaluminohydride (177 ml of a 0.5M solution in diglyme) was added dropwise such that the temperature of the reaction mixture did not exceed -65° C The reaction mixture was stirred for a further 2 hours at -70° C. poured onto ice The slurry obtained extracted with diethyl ether (3×75 ml) The combined ether extracts were washed with brine dried (MgSO4) The solvent was removed the residue dissolved in petroleum ether (BP 60-80° C.) washed once with aqueous saturated sodium bicarbonate, five times with water and twice with brine then dried Removal of the solvent gave an oil which was purified by chromatography on silica eluting with dichloromethane-hexane (1:1 v/v)

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

Procedure: Methyl 4-[2-(phenethyl)phenethyl]benzoate was prepared from 2-phenethylbenzaldehyde and 4-carboxybenzyltriphenylphosphonium bromide using a similar method to the described in Example 24 for the preparation of methyl 4-[3-(2-(phenethyl)phenyl)propyl]benzoate.

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

Procedure: Methyl 4-[2-(phenethyl)phenethyl]benzoate was prepared from 2-phenethylbenzaldehyde and 4-carboxybenzyltriphenylphosphonium bromide using a similar method to the described in Example 24 for the preparation of methyl 4-[3-(2-(phenethyl)phenyl)propyl]benzoate.