(4-chlorophenyl)-phenylmethanol

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

Procedure: Thionyl chloride (10 mL, 137 mmol) was added dropwise to 4-chlorobenzhydrol (12.66 g, 50 mmol) in CH2Cl2 (200 mL) under nitrogen over 15 min. After 18 h and solvent removal in vacuo, the crude product was dissolved in methylene chloride (250 mL) and washed with saturated NaHCO3 (3×50 mL), dried over Na2SO4, and concentrated in vacuo to a thin, amber oil (12.53 g). Upon standing at room temperature for 1 h, crystallization occured to give pure product (12.5 g, 88.4%) as a white solid, mp 61°-64° C. DCI/MS (M+1) 235. 400 MHz 1H NMR (CDCl3) δ: 7.35 (m, 8H), 6.05 (s, 1H). solvent removal in vacuo the crude product was dissolved in methylene chloride (250 mL) washed with saturated NaHCO3 (3×50 mL) dried over Na2SO4 concentrated in vacuo to a thin, amber oil (12.53 g) Upon standing at room temperature for 1 h crystallization

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

Procedure: 15.2 g (0.07 mole) of phenyl-(4-chlorophenyl)-ketone are dissolved in 30 ml of tetrahydrofuran and 10 ml of methanol. 1.32 g (0.035 mole) of sodium borohydride are gradually added, with stirring, and the exothermic reaction is maintained between 25° and 30° C. by cooling. After one hour ketone can no longer be detected by thin layer chromatography. The mixture is then extracted with water and chloroform, the chloroform is dried with sodium sulfate and removed in a rotary evaporator. The crude yield is 16.2 g (oil). Of this 15.5 g are distilled at 220° C. and 30 mbar in a bulb tube oven. 14.3 g of an oil are obtained which is more than 95% pure according to gas chromatography and solidifies into crystals on cooling. 13.3 g are recrystallised from a mixture of 25 ml of n-hexane and 5 ml of cyclohexane. The yield is 12.2 g; m.p. 58°-60° C. the exothermic reaction is maintained between 25° and 30° C. by cooling The mixture is then extracted with water and chloroform the chloroform is dried with sodium sulfate removed in a rotary evaporator Of this 15.5 g are distilled at 220° C.

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

Procedure: 15.2 g (0.07 mole) of phenyl-(4-chlorophenyl)-ketone are dissolved in 30 ml of tetrahydrofuran and 10 ml of methanol. 1.32 g (0.035 mole) of sodium borohydride are gradually added, with stirring, and the exothermic reaction is maintained between 25° and 30° C. by cooling. After one hour ketone can no longer be detected by thin layer chromatography. The mixture is then extracted with water and chloroform, the chloroform is dried with sodium sulfate and removed in a rotary evaporator. The crude yield is 16.2 g (oil). Of this 15.5 g are distilled at 220° C. and 30 mbar in a bulb tube oven. 14.3 g of an oil are obtained which is more than 95% pure according to gas chromatography and solidifies into crystals on cooling. 13.3 g are recrystallised from a mixture of 25 ml of n-hexane and 5 ml of cyclohexane. The yield is 12.2 g; m.p. 58°-60° C. the exothermic reaction is maintained between 25° and 30° C. by cooling The mixture is then extracted with water and chloroform the chloroform is dried with sodium sulfate removed in a rotary evaporator Of this 15.5 g are distilled at 220° C.

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

Procedure: To a solution of 1-[(4-chloro-phenyl)-phenyl-methyl]-piperazine (0.59 g, 2.08 mmol) in dry CH2Cl2 (40 ml) was added 3,3-diphenylpropanoic acid (0.472 g, 2.08 mmol) under nitrogen. To the reaction was added EDC (0.797 g, 4.16 mmol) and DMAP (cat) and the reaction mixture stirred under nitrogen at room temp. over night. The reaction was then concentrated under reduced pressure. The residue dissolved in ethyl acetate: water (10:1) (150 ml). The organic was washed with water (30 ml, 2×) and 10% NaOH (30 ml) and dried over MgSO4 and evaporated to dryness. The resulting residue was purified by column chromatography using hexane: ethyl acetate (3:1) to give desired product in 78% yield. The reaction was then concentrated under reduced pressure The residue dissolved in ethyl acetate: water (10:1) (150 ml) The organic was washed with water (30 ml, 2×) and 10% NaOH (30 ml) dried over MgSO4 evaporated to dryness The resulting residue was purified by column chromatography

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

Procedure: A mixture of 1-chloro-4-(chloro-phenyl-methyl)-benzene (4.12 g, 17.4 mmol) in butanone (20 ml), anhydrous piperazine (5.98 g, 69.6 mmol), anhydrous K2CO3 (2.40 g, 17.4 mmol) and KI (2.88 g, 17.4 mmol) was refluxed under nitrogen for 18 hours. The mixture was then cooled and filtered and the solvent removed in vacuo. The residue was dissolved in CH2Cl2 (100 ml) and washed with water (30 ml). Drying and removal of the solvent followed by chromatography (CH2Cl2:CH3OH:NH4OH 90:10:0.5) afforded desired product in 57% yield. D. Synthesis of 1-{4-[(4-Chloro-phenyl)-phenyl-methyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one was refluxed under nitrogen for 18 hours The mixture was then cooled filtered the solvent removed in vacuo The residue was dissolved in CH2Cl2 (100 ml) washed with water (30 ml) Drying removal of the solvent

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

Procedure: A mixture of 1-chloro-4-(chloro-phenyl-methyl)-benzene (4.12 g, 17.4 mmol) in butanone (20 ml), anhydrous piperazine (5.98 g, 69.6 mmol), anhydrous K2CO3 (2.40 g, 17.4 mmol) and KI (2.88 g, 17.4 mmol) was refluxed under nitrogen for 18 hours. The mixture was then cooled and filtered and the solvent removed in vacuo. The residue was dissolved in CH2Cl2 (100 ml) and washed with water (30 ml). Drying and removal of the solvent followed by chromatography (CH2Cl2:CH3OH:NH4OH 90:10:0.5) afforded desired product in 57% yield. D. Synthesis of 1-{4-[(4-Chloro-phenyl)-phenyl-methyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one was refluxed under nitrogen for 18 hours The mixture was then cooled filtered the solvent removed in vacuo The residue was dissolved in CH2Cl2 (100 ml) washed with water (30 ml) Drying removal of the solvent

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

Procedure: Thionyl chloride (10 mL, 137 mmol) was added dropwise to 4-chlorobenzhydrol (12.66 g, 50 mmol) in CH2Cl2 (200 mL) under nitrogen over 15 min. After 18 h and solvent removal in vacuo, the crude product was dissolved in methylene chloride (250 mL) and washed with saturated NaHCO3 (3×50 mL), dried over Na2SO4, and concentrated in vacuo to a thin, amber oil (12.53 g). Upon standing at room temperature for 1 h, crystallization occured to give pure product (12.5 g, 88.4%) as a white solid, mp 61°-64° C. DCI/MS (M+1) 235. 400 MHz 1H NMR (CDCl3) δ: 7.35 (m, 8H), 6.05 (s, 1H). solvent removal in vacuo the crude product was dissolved in methylene chloride (250 mL) washed with saturated NaHCO3 (3×50 mL) dried over Na2SO4 concentrated in vacuo to a thin, amber oil (12.53 g) Upon standing at room temperature for 1 h crystallization

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

Procedure: Thionyl chloride (10 mL, 137 mmol) was added dropwise to 4-chlorobenzhydrol (12.66 g, 50 mmol) in CH2Cl2 (200 mL) under nitrogen over 15 min. After 18 h and solvent removal in vacuo, the crude product was dissolved in methylene chloride (250 mL) and washed with saturated NaHCO3 (3×50 mL), dried over Na2SO4, and concentrated in vacuo to a thin, amber oil (12.53 g). Upon standing at room temperature for 1 h, crystallization occured to give pure product (12.5 g, 88.4%) as a white solid, mp 61°-64° C. DCI/MS (M+1) 235. 400 MHz 1H NMR (CDCl3) δ: 7.35 (m, 8H), 6.05 (s, 1H). solvent removal in vacuo the crude product was dissolved in methylene chloride (250 mL) washed with saturated NaHCO3 (3×50 mL) dried over Na2SO4 concentrated in vacuo to a thin, amber oil (12.53 g) Upon standing at room temperature for 1 h crystallization

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

Procedure: Thionyl chloride (10 mL, 137 mmol) was added dropwise to 4-chlorobenzhydrol (12.66 g, 50 mmol) in CH2Cl2 (200 mL) under nitrogen over 15 min. After 18 h and solvent removal in vacuo, the crude product was dissolved in methylene chloride (250 mL) and washed with saturated NaHCO3 (3×50 mL), dried over Na2 -SO4, and concentrated in vacuo to a thin, amber oil (12.53 g). Upon standing at room temperature for 1 h, crystallization occured to give pure product (12.5 g, 88.4%) as a white solid, mp 61°-64° C. DCI/MS (M+1) 235. 400 MHz 1H NMR (CDCl3)δ: 7.35 (m, 8H), 6.05 (s, 1H). solvent removal in vacuo the crude product was dissolved in methylene chloride (250 mL) washed with saturated NaHCO3 (3×50 mL) dried over Na2 -SO4 concentrated in vacuo to a thin, amber oil (12.53 g) Upon standing at room temperature for 1 h crystallization

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

Procedure: Thionyl chloride (10 mL, 137 mmol) was added dropwise to 4-chlorobenzhydrol (12.66 g, 50 mmol) in CH2Cl2 (200 mL) under nitrogen over 15 min. After 18 h and solvent removal in vacuo, the crude product was dissolved in methylene chloride (250 mL) and washed with saturated NaHCO3 (3×50 mL), dried over Na2 -SO4, and concentrated in vacuo to a thin, amber oil (12.53 g). Upon standing at room temperature for 1 h, crystallization occured to give pure product (12.5 g, 88.4%) as a white solid, mp 61°-64° C. DCI/MS (M+1) 235. 400 MHz 1H NMR (CDCl3)δ: 7.35 (m, 8H), 6.05 (s, 1H). solvent removal in vacuo the crude product was dissolved in methylene chloride (250 mL) washed with saturated NaHCO3 (3×50 mL) dried over Na2 -SO4 concentrated in vacuo to a thin, amber oil (12.53 g) Upon standing at room temperature for 1 h crystallization