2-(4-chlorophenyl)propanal

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3.9 g (0.023 mole) of 2-(4-chlorophenyl)propionaldehyde in 25 mL of 1,4-dioxane is added in one portion 9.0 g (0.026 mole) of (carbethoxymethylene)triphenylphosphorane. The reaction mixture is stirred for approximately 16 hours at ambient temperature after which the solvent is evaporated under reduced pressure, leaving a residue which is then dissolved in ethyl acetate. Approximately 10 g of silica gel is mixed with the resulting solution. The solvent is evaporated from this mixture, and the residue is placed in a sintered glass filter. The silica gel is then eluted with 100 mL of heptane/ethyl acetate (3:1). These solvents are evaporated under reduced pressure, leaving a residue. This residue is dissolved in 30 mL of heptane/ethyl acetate (9:1), treated with 5 g of silica gel, and filtered. The filtrate is evaporated under reduced pressure, leaving ethyl 4-(4-chlorophenyl)-2-pentenoate as a residue. is evaporated under reduced pressure leaving a residue which Approximately 10 g of silica gel is mixed with the resulting solution The solvent is evaporated from this mixture filter The silica gel is then eluted with 100 mL of heptane/ethyl acetate (3:1) These solvents are evaporated under reduced pressure leaving a residue treated with 5 g of silica gel filtered The filtrate is evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 19.8 g (0.092 mole) of pyridinium chlorochromate in 80 mL of methylene chloride is added a solution of 7.8 g (0.046 mole) of 2-(4-chlorophenyl)propanol in 20 mL of methylene chloride. After one hour this mixture is diluted with 100 mL of diethyl ether, and the remaining solution is decanted from the insoluble material. Additional diethyl ether is added to the solids, and, after being mixed thoroughly, the solution is decanted from the solids and combined with the original solution. The combination is washed sequentially with 10 mL of a 10% aqueous solution of sodium hydroxide, 10 mL of 10% hydrochloric acid, and finally with 10 mL of water. After being dried over an hydrous magnesium sulfate, this solution is evaporated under reduced pressure, leaving a residue. This residue is passed through a column of silica gel, eluting with ethyl acetate/hexane (5:95). Product-containing fractions are combined, and the solvent is evaporated from the combined fractions under reduced pressure, leaving 2-(4-chlorophenyl)propionaldehyde as the residue. the remaining solution is decanted from the insoluble material Additional diethyl ether is added to the solids after being mixed thoroughly the solution is decanted from the solids The combination is washed sequentially with 10 mL of a 10% aqueous solution of sodium hydroxide, 10 mL of 10% hydrochloric acid After being dried over an hydrous magnesium sulfate this solution is evaporated under reduced pressure leaving a residue eluting with ethyl acetate/hexane (5:95) the solvent is evaporated from the combined fractions under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The synthesis of intermediates leading to different values of m and X is within the capability of one skilled in the art. Example 3 details the method of making the compound wherein X is --CH(CH3)-- and m is 2. This synthesis starts with the reduction of 2-(4-chlorophenyl)propionic acid with lithium aluminum hydride, producing 2-(4-chlorophenyl)propanol. Oxidation of this alcohol with pyridinium chlorochromate in methylene chloride produces 2-(4-chlorophenyl)propionaldehyde. This aldehyde is then reacted with (carbethoxymethylene)triphenylphosphorane, yielding ethyl 4-(4-chlorophenyl)-2-pentenoate. Hydrogenation of this ester in the presence of platinum oxide produces ethyl 4-(4-chlorophenyl)pentanoate which is then hydrolyzed with sodium hydroxide to the corresponding pentanoic acid (II). The remaining steps of this synthesis are shown in Schema 1.