2-(4-chlorophenyl)-2-methylpropanal

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

Procedure: A solution of triphenyl phosphine (89.34 g, 0.34 mol) in methylene chloride is added dropwise to a mixture of zinc powder (22.27 g, 0.34 mol) and carbon tetrabromide (112.8 g, 0.34 mol) in methylene chloride at 20° C. over one hour. The resultant mixture is stirred at room temperature overnight, treated dropwise with a solution of 2-(p-chlorophenyl)-2-methylpropionaldehyde (31.1 g, 0.17 mol) in methylene chloride over 20 minutes, refluxed for 2 days, and poured into petroleum ether. The organic mixture is filtered through diatomaceous earth and concentrated in vacuo to obtain a residue. The residue is distilled to give the title product as an oil (38.5 g, bp 121-123° C./0.3 mm Hg, 66.8% yield). refluxed for 2 days The organic mixture is filtered through diatomaceous earth concentrated in vacuo to obtain a residue The residue is distilled

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

Procedure: Diisobutylaluminum hydride (0.236 mol, 236 mL of a 1M solution in hexane) is added over 90 minutes to a solution of p-chloro-α-methylhydratroponitrile (32.6 g, 0.181 mol) in diethyl ether under nitrogen at 0° C. After the addition is complete, water and 6N hydrochloric acid are added to the reaction mixture while maintaining the temperature below 30° C. The resultant aqueous solution is stirred overnight at room temperature and extracted with diethyl ether The organic extracts are combined, washed sequentially with 2N hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give the title product as an oil (31.1 g, 94% yield). After the addition while maintaining the temperature below 30° C extracted with diethyl ether The organic extracts washed sequentially with 2N hydrochloric acid and water dried over anhydrous sodium sulfate concentrated in vacuo

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

Procedure: In the same manner as described in Synthesis Example 2, the equivalent mixture of α,α-dimethyl-(4-chlorophenyl)acetaldehyde and 3-phenoxyacetophenone was treated to give 1-(3-phenoxyphenyl)-4-(4-chlorophenyl)-4-methylpentane. In the same manner as described in Synthesis Example 2 was treated

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

Procedure: In the same manner as described in Synthesis Example 2, the equivalent mixture of α,α-dimethyl-(4-chlorophenyl)acetaldehyde and 3-phenoxyacetophenone was treated to give 1-(3-phenoxyphenyl)-4-(4-chlorophenyl)-4-methylpentane. In the same manner as described in Synthesis Example 2 was treated

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

Procedure: To a stirring solution of 41.7 grams (0.226 mole) of 2-methyl-2-(4-chlorophenyl)propanol in 100 mL of dimethyl sulfoxide is added 126 mL (0.904 mole) of triethylamine. A solution of 63.0 grams (0.452 mole) of triethylamine-sulfur trioxide complex in 300 mL of dimethyl sulfoxide is then added portionwise during a 15 minute period. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about five hours. The reaction mixture is then poured into about 500 mL of ice, and made acidic with aqueous 2N hydrochloric acid. The mixture is then extracted with two 100 mL portions of diethyl ether. The combined extracts are dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 22.9 grams of 2-methyl-2-(4-chlorophenyl)propanaldehyde. The NMR spectrum is consistent with the proposed structure. Upon completion of addition The mixture is then extracted with two 100 mL portions of diethyl ether The combined extracts are dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

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

Procedure: To a stirring solution of 41.7 grams (0.226 mole) of 2-methyl-2-(4-chlorophenyl)propanol in 100 mL of dimethyl sulfoxide is added 126 mL (0.904 mole) of triethylamine. A solution of 63.0 grams (0.452 mole) of triethylamine-sulfur trioxide complex in 300 mL of dimethyl sulfoxide is then added portionwise during a 15 minute period. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about five hours. The reaction mixture is then poured into about 500 mL of ice, and made acidic with aqueous 2N hydrochloric acid. The mixture is then extracted with two 100 mL portions of diethyl ether. The combined extracts are dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 22.9 grams of 2-methyl-2-(4-chlorophenyl)propanaldehyde. The NMR spectrum is consistent with the proposed structure. Upon completion of addition The mixture is then extracted with two 100 mL portions of diethyl ether The combined extracts are dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

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

Procedure: In the same manner as described in Synthesis Example 2, the equivalent mixture of α, α-dimethyl-(4-chlorophenyl)acetaldehyde and 3-phenoxyacetophenone was treated to give 1-(3-phenoxyphenyl)-4-(4-chlorophenyl)-4-methylpentane. In the same manner as described in Synthesis Example 2 was treated

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

Procedure: In the same manner as described in Synthesis Example 2, the equivalent mixture of α,α-dimethyl-(4-chlorophenyl)acetaldehyde and 3-phenoxyacetophenone was treated to give 1-(3-phenoxyphenyl)-4-(4-chlorophenyl)-4-methylpentane. In the same manner as described in Synthesis Example 2 was treated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 15.04 g of 2-diethylphosphono-2-ethoxyacetic acid-ethyl ester in 50 ml of tetrahydrofuran is mixed while being cooled with ice within 20 minutes with 30 ml of a 2 M solution of lithium diisopropylamide in tetrahydrofuran-heptane-toluene, and it is stirred for 15 minutes at 0° C. Within 30 minutes, a solution of 10.2 g of 2-(4-chlorophenyl)-2-methylpropanal in 50 ml of tetrahydrofuran is added in drops thereto at 0° C. After 20 hours at room temperature, 2N sulfuric acid is added, it is extracted with ethyl acetate, dried (Na2SO4) and concentrated by evaporation. The crude product is saponified with 200 ml of 2 M sodium hydroxide solution/400 ml of ethanol. 13.8 g of acid, which is refluxed for 3 hours with 300 ml of 2N sulfuric acid and 100 ml of glacial acetic acid while being stirred vigorously, is obtained. After extraction with ethyl acetate and washing with water, 10.9 g of 4-(4-chlorophenyl)-4-methyl-2-oxo-valeric acid is obtained as a red oil. Within 30 minutes at 0° C After 20 hours at room temperature it is extracted with ethyl acetate dried (Na2SO4) concentrated by evaporation 13.8 g of acid, which is refluxed for 3 hours with 300 ml of 2N sulfuric acid and 100 ml of glacial acetic acid while being stirred vigorously is obtained After extraction with ethyl acetate washing with water

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 15.04 g of 2-diethylphosphono-2-ethoxyacetic acid-ethyl ester in 50 ml of tetrahydrofuran is mixed while being cooled with ice within 20 minutes with 30 ml of a 2 M solution of lithium diisopropylamide in tetrahydrofuran-heptane-toluene, and it is stirred for 15 minutes at 0° C. Within 30 minutes, a solution of 10.2 g of 2-(4-chlorophenyl)-2-methylpropanal in 50 ml of tetrahydrofuran is added in drops thereto at 0° C. After 20 hours at room temperature, 2N sulfuric acid is added, it is extracted with ethyl acetate, dried (Na2SO4) and concentrated by evaporation. The crude product is saponified with 200 ml of 2 M sodium hydroxide solution/400 ml of ethanol. 13.8 g of acid, which is refluxed for 3 hours with 300 ml of 2N sulfuric acid and 100 ml of glacial acetic acid while being stirred vigorously, is obtained. After extraction with ethyl acetate and washing with water, 10.9 g of 4-(4-chlorophenyl)-4-methyl-2-oxo-valeric acid is obtained as a red oil. Within 30 minutes at 0° C After 20 hours at room temperature it is extracted with ethyl acetate dried (Na2SO4) concentrated by evaporation 13.8 g of acid, which is refluxed for 3 hours with 300 ml of 2N sulfuric acid and 100 ml of glacial acetic acid while being stirred vigorously is obtained After extraction with ethyl acetate washing with water

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 15.04 g of 2-diethylphosphono-2-ethoxyacetic acid-ethyl ester in 50 ml of tetrahydrofuran is mixed while being cooled with ice within 20 minutes with 30 ml of a 2 M solution of lithium diisopropylamide in tetrahydrofuran-heptane-toluene, and it is stirred for 15 minutes at 0° C. Within 30 minutes, a solution of 10.2 g of 2-(4-chlorophenyl)-2-methylpropanal in 50 ml of tetrahydrofuran is added in drops thereto at 0° C. After 20 hours at room temperature, 2N sulfuric acid is added, it is extracted with ethyl acetate, dried (Na2SO4) and concentrated by evaporation. The crude product is saponified with 200 ml of 2 M sodium hydroxide solution/400 ml of ethanol. 13.8 g of acid, which is refluxed for 3 hours with 300 ml of 2N sulfuric acid and 100 ml of glacial acetic acid while being stirred vigorously, is obtained. After extraction with ethyl acetate and washing with water, 10.9 g of 4-(4-chlorophenyl)-4-methyl-2-oxo-valeric acid is obtained as a red oil. Within 30 minutes at 0° C After 20 hours at room temperature it is extracted with ethyl acetate dried (Na2SO4) concentrated by evaporation 13.8 g of acid, which is refluxed for 3 hours with 300 ml of 2N sulfuric acid and 100 ml of glacial acetic acid while being stirred vigorously is obtained After extraction with ethyl acetate washing with water

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

Procedure: A solution of triphenyl phosphine (89.34 g, 0.34 mol) in methylene chloride is added dropwise to a mixture of zinc powder (22.27 g, 0.34 mol) and carbon tetrabromide (112.8 g, 0.34 mol) in methylene chloride at 20° C. over one hour. The resultant mixture is stirred at room temperature overnight, treated dropwise with a solution of 2-(p-chlorophenyl)-2-methylpropionaldehyde (31.1 g, 0.17 mol) in methylene chloride over 20 minutes, refluxed for 2 days, and poured into petroleum ether. The organic mixture is filtered through diatomaceous earth and concentrated in vacuo to obtain a residue. The residue is distilled to give the title product as an oil (38.5 g, bp 121-123° C./0.3 mm Hg, 66.8% yield). refluxed for 2 days The organic mixture is filtered through diatomaceous earth concentrated in vacuo to obtain a residue The residue is distilled