2-(4-chlorophenyl)propan-1-ol

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

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

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

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

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

Procedure: To 833 ml. of a chilled solution (0° C.) of 1M diborane in tetrahydrofuran is added dropwise a solution of 96 g. of 2-(p-chlorophenoxy)propionic acid in 500 ml. of tetrahydrofuran. The reaction mixture is stirred for 2 days at room temperature and then poured onto 2 kg. of ice/water. The resulting mixture is extracted with diethyl ether and the extract is washed with water and dried over MgSO4. The solvent is removed under vacuum and the residual liquid is distilled to give 83 g. (b.p. 116°-120° C./0.1 mm.) of product. poured onto 2 kg The resulting mixture is extracted with diethyl ether the extract is washed with water dried over MgSO4 The solvent is removed under vacuum the residual liquid is distilled to give 83 g

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

Procedure: 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

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

Procedure: To a suspension of 3.8 g (0.10 mole) of lithium aluminum hydride in 50 mL of tetrahydrofuran is added dropwise a solution of 18.4 g (0.10 mole) of 2-(4-chlorophenyl)propionic acid in 200 mL of tetrahydrofuran. This reaction mixture is allowed to stir at ambient temperature for a period of approximately 16 hours after which it is cooled by an ice/water bath. To the cooled reaction mixture are added in sequence 4 mL of water, 4 mL of a 10% aqueous solution of sodium hydroxide, and 12 mL of water. The mixture is then filtered, and the filter cake is washed with diethyl ether. The diethyl ether wash is combined with the filtrate, and the combination is dried over anhydrous magnesium sulfate. The solvents are then evaporated under reduced pressure, leaving 2-(4-chlorophenyl)propanol as a residue. is cooled by an ice/water bath To the cooled reaction mixture The mixture is then filtered the filter cake is washed with diethyl ether The diethyl ether wash the combination is dried over anhydrous magnesium sulfate The solvents are then evaporated under reduced pressure

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

Procedure: 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. The synthesis of intermediates