(4-chlorophenyl)-phenylmethanone

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: A solution of 25.5 g (0.08 mol) of 20% butyl lithium in n-hexane in 50 ml. of anhydrous diethyl ether was added at room temperature to a solution of 5 g (0.06 mol) of 1-methylimidazole in 50 ml. of anhydrous diethyl ether. The reaction mixture was stirred for one hour and then a solution of 15.6 g (0.07 mol) of 4-chlorobenzophenone in diethyl ether was added dropwise. The reaction mixture was stirred for 3 hours and it was then poured into a mixture of ice and water. The solid matter was filtered off and crystallised from ethanol. α-(p-Chlorophenyl)-1-methyl-α-phenylimidazole-2-methanol was obtained. Melting point 185°-186° C. The reaction mixture was stirred for 3 hours The solid matter was filtered off crystallised from ethanol

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

Procedure: A solution of 25.5 g (0.08 mol) of 20% butyl lithium in n-hexane in 50 ml. of anhydrous diethyl ether was added at room temperature to a solution of 5 g (0.06 mol) of 1-methylimidazole in 50 ml. of anhydrous diethyl ether. The reaction mixture was stirred for one hour and then a solution of 15.6 g (0.07 mol) of 4-chlorobenzophenone in diethyl ether was added dropwise. The reaction mixture was stirred for 3 hours and it was then poured into a mixture of ice and water. The solid matter was filtered off and crystallised from ethanol. α-(p-Chlorophenyl)-1-methyl-α-phenylimidazole-2-methanol was obtained. Melting point 185°-186° C. The reaction mixture was stirred for 3 hours The solid matter was filtered off crystallised from ethanol

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

Procedure: A solution of 20 ml. 20% butyl lithium in n-hexane (0.043 mol) in 30 ml. of diethyl ether was added dropwise under a nitrogen atmosphere to a solution of 5.5 g (0.032 mol) of 1-phenethylimidazole (J. Am. Chem. Soc., 71, 4000 (1949)) in 100 ml. of diethyl ether. After the addition was completed, the reaction mixture was stirred for another hour at room temperature. Then a solution of 7.8 g (0.036 mol) of 4-chlorobenzophenone in 75 ml. of anhydrous diethyl ether was added dropwise. The reaction mixture was stirred for 3 hours and it was then poured into 200 ml of ice-water. The ethereal layer was separated off, dried over sodium sulphate and the ether was distilled off. The residue was crystallised from a mixture of ethanol and petroleum ether (boiling range 40°-60° C.). α-(p-Chlorophenyl)-1-(phenethyl-α-phenylimidazole-2-methanol was obtained. Melting point 164°-165° C. After the addition The reaction mixture was stirred for 3 hours The ethereal layer was separated off dried over sodium sulphate the ether was distilled off The residue was crystallised from a mixture of ethanol and petroleum ether (boiling range 40°-60° C.)

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

Procedure: A solution of 20 ml. 20% butyl lithium in n-hexane (0.043 mol) in 30 ml. of diethyl ether was added dropwise under a nitrogen atmosphere to a solution of 5.5 g (0.032 mol) of 1-phenethylimidazole (J. Am. Chem. Soc., 71, 4000 (1949)) in 100 ml. of diethyl ether. After the addition was completed, the reaction mixture was stirred for another hour at room temperature. Then a solution of 7.8 g (0.036 mol) of 4-chlorobenzophenone in 75 ml. of anhydrous diethyl ether was added dropwise. The reaction mixture was stirred for 3 hours and it was then poured into 200 ml of ice-water. The ethereal layer was separated off, dried over sodium sulphate and the ether was distilled off. The residue was crystallised from a mixture of ethanol and petroleum ether (boiling range 40°-60° C.). α-(p-Chlorophenyl)-1-(phenethyl-α-phenylimidazole-2-methanol was obtained. Melting point 164°-165° C. After the addition The reaction mixture was stirred for 3 hours The ethereal layer was separated off dried over sodium sulphate the ether was distilled off The residue was crystallised from a mixture of ethanol and petroleum ether (boiling range 40°-60° C.)

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

Procedure: To a solution of 11.8 g. of 1-[(benzyloxy)methyl]imidazole in 100 ml. of anhydrous tetrahydrofuran and 50 ml. of anhydrous diethyl ether a solution of 38 ml. of a 20% butyllithium suspension in hexane dissolved in 75 ml. of anhydrous diethyl ether was added drop-wise with stirring at room temperature. Thereafter a solution of 14.6 g. of 4-chlorobenzophenone in 100 ml. of anhydrous tetrahydrofuran and 50 ml. of anhydrous diethyl ether was added drop-wise at room temperature. The mixture was kept for three hours and then extracted with a dilute acid solution. The acidic aqueous layer was made alkaline with 2 N sodium hydroxide solution and extracted with diethyl ether. Part of the ether was removed by evaporation and the residue washed with water. The ether solution was again concentrated and the desired compound crystallised from a mixture of toluene and petroleum ether (boiling range 28°-40° C.). Melting point of the product was 114.5°-117° C. extracted with a dilute acid solution extracted with diethyl ether Part of the ether was removed by evaporation the residue washed with water The ether solution was again concentrated the desired compound crystallised from a mixture of toluene and petroleum ether (boiling range 28°-40° C.) was 114.5°-117° C.

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

Procedure: To a solution of 11.8 g. of 1-[(benzyloxy)methyl]imidazole in 100 ml. of anhydrous tetrahydrofuran and 50 ml. of anhydrous diethyl ether a solution of 38 ml. of a 20% butyllithium suspension in hexane dissolved in 75 ml. of anhydrous diethyl ether was added drop-wise with stirring at room temperature. Thereafter a solution of 14.6 g. of 4-chlorobenzophenone in 100 ml. of anhydrous tetrahydrofuran and 50 ml. of anhydrous diethyl ether was added drop-wise at room temperature. The mixture was kept for three hours and then extracted with a dilute acid solution. The acidic aqueous layer was made alkaline with 2 N sodium hydroxide solution and extracted with diethyl ether. Part of the ether was removed by evaporation and the residue washed with water. The ether solution was again concentrated and the desired compound crystallised from a mixture of toluene and petroleum ether (boiling range 28°-40° C.). Melting point of the product was 114.5°-117° C. extracted with a dilute acid solution extracted with diethyl ether Part of the ether was removed by evaporation the residue washed with water The ether solution was again concentrated the desired compound crystallised from a mixture of toluene and petroleum ether (boiling range 28°-40° C.) was 114.5°-117° C.

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner to Example 1, a mixture of 4-chlorobenzophenone (8.0 g) and 1-(3-aminopropyl)imidazole (4.6 g) was heated at 130° C. for 12 hours. The mixture was cooled, dissolved in absolute ethanol (100 ml), treated with sodium borohydride (2.8 g) and the mixture boiled under reflux for 8 hours. The oil obtained after work-up, using dichloromethane as the extracting solvent, was distilled to give N-[α-(4-chlorophenyl)benzyl]-3-(imidazol-1-yl)propylamine, b.p. 240° C. (0.3 mmHg). The mixture was cooled under reflux for 8 hours The oil obtained after work-up was distilled

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

Procedure: In a nitrogen-atmosphere glovebox, a microwave vial equipped with a magnetic stir bar was charged with 4-chlorobenzophenone (100 mg, 0.462 mmol, 1 equivalent), sodium nitrite (63.7 mg, 0.923 mmol, 2 equivalents), tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3) (0.005 or 0.0025 equivalents) and 7,7,9,9-tetramethyl-8-(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)-1,4-dioxa-8-phosphaspiro[4.5]decane (0.012 or 0.006 equivalents, respectively). The solids were slurried in t-butyl alcohol (0.84 mL) before adding tris[2-(2-methoxyethoxyl)ethyl]amine (TDA-1) (7.4 μL, 0.023 mmol, 0.05 equivalents). The vial was sealed with a crimp top and placed in a heating block at 130° C. After indicated reaction time, the vial was cooled to room temperature and brought out of the glovebox. The reaction solution was diluted with tetrahydrofuran (2 mL) and filtered through a pad of diatomaceous earth into a tared 125-mL Erlenmeyer flask. The vial was rinsed with tetrahydrofuran (5×1 mL) before the filter cake was washed with tetrahydrofuran (5 mL). A wt % analysis was performed on the filtrate and an assay yield was measured. In a nitrogen-atmosphere glovebox, a microwave vial equipped with a magnetic stir bar The vial was sealed with a crimp top placed in a heating block at 130° C reaction time filtered through a pad of diatomaceous earth into a tared 125-mL Erlenmeyer flask The vial was rinsed with tetrahydrofuran (5×1 mL) before the filter cake was washed with tetrahydrofuran (5 mL) an assay yield

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

Procedure: In a nitrogen-atmosphere glovebox, a microwave vial equipped with a magnetic stir bar was charged with 4-chlorobenzophenone (100 mg, 0.462 mmol, 1 equivalent), sodium nitrite (63.7 mg, 0.923 mmol, 2 equivalents), tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3) (0.005 or 0.0025 equivalents) and 7,7,9,9-tetramethyl-8-(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)-1,4-dioxa-8-phosphaspiro[4.5]decane (0.012 or 0.006 equivalents, respectively). The solids were slurried in t-butyl alcohol (0.84 mL) before adding tris[2-(2-methoxyethoxyl)ethyl]amine (TDA-1) (7.4 μL, 0.023 mmol, 0.05 equivalents). The vial was sealed with a crimp top and placed in a heating block at 130° C. After indicated reaction time, the vial was cooled to room temperature and brought out of the glovebox. The reaction solution was diluted with tetrahydrofuran (2 mL) and filtered through a pad of diatomaceous earth into a tared 125-mL Erlenmeyer flask. The vial was rinsed with tetrahydrofuran (5×1 mL) before the filter cake was washed with tetrahydrofuran (5 mL). A wt % analysis was performed on the filtrate and an assay yield was measured. In a nitrogen-atmosphere glovebox, a microwave vial equipped with a magnetic stir bar The vial was sealed with a crimp top placed in a heating block at 130° C reaction time filtered through a pad of diatomaceous earth into a tared 125-mL Erlenmeyer flask The vial was rinsed with tetrahydrofuran (5×1 mL) before the filter cake was washed with tetrahydrofuran (5 mL) an assay yield