ethyl 4-sulfanylbenzoate

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

Procedure: To a stirred solution of 5.6 parts of 1-(6-chloro-3-pyridazinyl)-4-piperidinepropanol, 4.2 parts of ethyl 4-mercaptobenzoate and 6 parts of triphenylposphine in 135 parts of tetrahydrofuran was added dropwise a solution of 4 parts of diethyl diazenedicarboxylate in 45 parts of tetrahydrofuran at 20° C. Upon complete addition, stirring was continued overnight at this temperature. The reaction mixture was evaporated and the residue was taken up in water. The product was ectracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (99:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried, yielding 1.3 parts (13.5%) of ethyl 4-[[3-[1-(6-chloro-3-pyridazinyl)-4-piperidinyl]propyl]thio]benzoate; mp. 96.3° C. (comp. 164). Upon complete addition The reaction mixture was evaporated The extract was dried filtered evaporated The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (99:1 by volume) as eluent The pure fractions were collected the eluent was evaporated The residue was crystallized from 2,2'-oxybispropane The product was filtered off dried

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

Procedure: Ethyl-4-mercaptobenzoate was prepared by treating 4-mercaptobenzoic acid (1.50 g, 9.73 mmol) with ethanol (97 mL) in the presence of catalytic concentrated sulfuric acid under a nitrogen atmosphere. The reaction was heated at reflux for three hours. The volume of the reaction was reduced to 10 mL under reduced pressure and then partitioned between water (100 mL) and ethyl acetate (100 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL), and the combined organic solutions were washed with water (75 mL) and saturated aqueous sodium bicarbonate (2×75 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide an oil. The oil was dissolved in dichloromethane (100 mL), and the resulting solution was extracted with saturated aqueous sodium carbonate (3×100 mL). The combined extracts were washed with dichloromethane (3×50 mL) and then treated with concentrated hydrochloric acid to adjust to pH 7. The solution was then extracted with dichloromethane (3×100 mL), and the combined extracts were washed with water (50 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 1.23 g of ethyl-4-mercaptobenzoate as a colorless oil. Ethyl-4-mercaptobenzoate was prepared The reaction was heated at reflux for three hours partitioned between water (100 mL) and ethyl acetate (100 mL) The aqueous layer was extracted with ethyl acetate (3×100 mL) the combined organic solutions were washed with water (75 mL) and saturated aqueous sodium bicarbonate (2×75 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to provide an oil the resulting solution was extracted with saturated aqueous sodium carbonate (3×100 mL) The combined extracts were washed with dichloromethane (3×50 mL) treated with concentrated hydrochloric acid The solution was then extracted with dichloromethane (3×100 mL) the combined extracts were washed with water (50 mL) dried over magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a stirred solution of 5.6 parts of 1-(6-chloro-3-pyridazinyl)-4-piperidinepropanol, 4.2 parts of ethyl 4-mercaptobenzoate and 6 parts of triphenylposphine in 135 parts of tetrahydrofuran was added dropwise a solution of 4 parts of diethyl diazenedicarboxylate in 45 parts of tetrahydrofuran at 20° C. Upon complete addition, stirring was continued overnight at this temperature. The reaction mixture was evaporated and the residue was taken up in water. The product was ectracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (99:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried, yielding 1.3 parts (13.5%) of ethyl 4-[[3-[1-(6-chloro-3-pyridazinyl)-4-piperidinyl]propyl]thio]benzoate; mp. 96.3° C. (comp. 164). Upon complete addition The reaction mixture was evaporated The extract was dried filtered evaporated The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (99:1 by volume) as eluent The pure fractions were collected the eluent was evaporated The residue was crystallized from 2,2'-oxybispropane The product was filtered off dried

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

Procedure: To a stirred solution of 5.6 parts of 1-(6-chloro-3-pyridazinyl)-4-piperidinepropanol, 4.2 parts of ethyl 4-mercaptobenzoate and 6 parts of triphenylposphine in 135 parts of tetrahydrofuran was added dropwise a solution of 4 parts of diethyl diazenedicarboxylate in 45 parts of tetrahydrofuran at 20° C. Upon complete addition, stirring was continued overnight at this temperature. The reaction mixture was evaporated and the residue was taken up in water. The product was ectracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (99:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried, yielding 1.3 parts (13.5%) of ethyl 4-[[3-[1-(6-chloro-3-pyridazinyl)-4-piperidinyl]propyl]thio]benzoate; mp. 96.3° C. (comp. 164). Upon complete addition The reaction mixture was evaporated The extract was dried filtered evaporated The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (99:1 by volume) as eluent The pure fractions were collected the eluent was evaporated The residue was crystallized from 2,2'-oxybispropane The product was filtered off dried

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

Procedure: A solution of 5.9 g of p-mercaptobenzoic acid ethyl ester (prepared according to the procedure found in J. Chem. Soc., 1963, 1947-1954) in 30 ml of dimethylformamide is added dropwise to a slurry of 1.55 g of 50% sodium hydride (dispersion in mineral oil) in 30 ml of dimethylformamide. This mixture is stirred at room temperature for 0.5 hour under nitrogen atmosphere, and added dropwise to a solution of 9.78 g of 3-(2-methylsulfonyloxyethyl)-2-(3-pyridyl)-indole in 60 ml of dimethylformamide at -10°. This mixture is stirred at room temperature overnight and poured into 1 liter of ice-water. This is extraced several times with ether. The ether extract is washed with water, dried over MgSO4 and evaporated in vacuo to give 3-[2-(4-ethoxycarbonylphenylthio)-ethyl]-2-(3-pyridyl-indole. This mixture is stirred at room temperature overnight The ether extract is washed with water dried over MgSO4 evaporated in vacuo

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

Procedure: A solution of 5.9 g of p-mercaptobenzoic acid ethyl ester (prepared according to the procedure found in J. Chem. Soc., 1963, 1947-1954) in 30 ml of dimethylformamide is added dropwise to a slurry of 1.55 g of 50% sodium hydride (dispersion in mineral oil in 30 ml of dimethylformamide. This mixture is stirred at room temperature for 0.5 hour under nitrogen atmosphere. This solution is added dropwise to a solution of 9.78 g of 1-(2-methylsulfonyloxyethyl)-2-(3-pyridyl)-3-methylindole in 60 ml of dimethylformamide at -10°. This mixture is stirred at room temperature overnight and poured into 1 liter of ice-water. This is extracted several times with ether (ca 1 liter total). The ether extract is washed with water (3×200 ml), dried over MgSO4 and evaporated in vacuo yielding 1-[2-(4-ethoxycarbonylphenylthio)ethyl]-2-(3-pyridyl)-3-methylindole as an oil; NMR (CDCl3) confirms the structure. This mixture is stirred at room temperature overnight This is extracted several times with ether (ca 1 liter total) The ether extract is washed with water (3×200 ml) dried over MgSO4 evaporated in vacuo

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

Procedure: Ethyl-4-mercaptobenzoate was prepared by treating 4-mercaptobenzoic acid (1.50 g, 9.73 mmol) with ethanol (97 mL) in the presence of catalytic concentrated sulfuric acid under a nitrogen atmosphere. The reaction was heated at reflux for three hours. The volume of the reaction was reduced to 10 mL under reduced pressure and then partitioned between water (100 mL) and ethyl acetate (100 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL), and the combined organic solutions were washed with water (75 mL) and saturated aqueous sodium bicarbonate (2×75 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide an oil. The oil was dissolved in dichloromethane (100 mL), and the resulting solution was extracted with saturated aqueous sodium carbonate (3×100 mL). The combined extracts were washed with dichloromethane (3×50 mL) and then treated with concentrated hydrochloric acid to adjust to pH 7. The solution was then extracted with dichloromethane (3×100 mL), and the combined extracts were washed with water (50 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 1.23 g of ethyl-4-mercaptobenzoate as a colorless oil. Ethyl-4-mercaptobenzoate was prepared The reaction was heated at reflux for three hours partitioned between water (100 mL) and ethyl acetate (100 mL) The aqueous layer was extracted with ethyl acetate (3×100 mL) the combined organic solutions were washed with water (75 mL) and saturated aqueous sodium bicarbonate (2×75 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to provide an oil the resulting solution was extracted with saturated aqueous sodium carbonate (3×100 mL) The combined extracts were washed with dichloromethane (3×50 mL) treated with concentrated hydrochloric acid The solution was then extracted with dichloromethane (3×100 mL) the combined extracts were washed with water (50 mL) dried over magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: Ethyl-4-mercaptobenzoate was prepared by treating 4-mercaptobenzoic acid (1.50 g, 9.73 mmol) with ethanol (97 mL) in the presence of catalytic concentrated sulfuric acid under a nitrogen atmosphere. The reaction was heated at reflux for three hours. The volume of the reaction was reduced to 10 mL under reduced pressure and then partitioned between water (100 mL) and ethyl acetate (100 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL), and the combined organic solutions were washed with water (75 mL) and saturated aqueous sodium bicarbonate (2×75 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide an oil. The oil was dissolved in dichloromethane (100 mL), and the resulting solution was extracted with saturated aqueous sodium carbonate (3×100 mL). The combined extracts were washed with dichloromethane (3×50 mL) and then treated with concentrated hydrochloric acid to adjust to pH 7. The solution was then extracted with dichloromethane (3×100 mL), and the combined extracts were washed with water (50 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 1.23 g of ethyl-4-mercaptobenzoate as a colorless oil. Ethyl-4-mercaptobenzoate was prepared The reaction was heated at reflux for three hours partitioned between water (100 mL) and ethyl acetate (100 mL) The aqueous layer was extracted with ethyl acetate (3×100 mL) the combined organic solutions were washed with water (75 mL) and saturated aqueous sodium bicarbonate (2×75 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to provide an oil the resulting solution was extracted with saturated aqueous sodium carbonate (3×100 mL) The combined extracts were washed with dichloromethane (3×50 mL) treated with concentrated hydrochloric acid The solution was then extracted with dichloromethane (3×100 mL) the combined extracts were washed with water (50 mL) dried over magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a stirred solution of 5.6 parts of 1-(6-chloro-3-pyridazinyl)-4-piperidinepropanol, 4.2 parts of ethyl 4-mercaptobenzoate and 6 parts of triphenylposphine in 135 parts of tetrahydrofuran was added dropwise a solution of 4 parts of diethyl diazenedicarboxylate in 45 parts of tetrahydrofuran at 20° C. Upon complete addition, stirring was continued overnight at this temperature. The reaction mixture was evaporated and the residue was taken up in water. The product was ectracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (99:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried, yielding 1.3 parts (13.5%) of ethyl 4-[[3-[1-(6-chloro-3-pyridazinyl)-4-piperidinyl]propyl]thio]benzoate; mp. 96.3° C. (comp. 164). Upon complete addition The reaction mixture was evaporated The extract was dried filtered evaporated The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (99:1 by volume) as eluent The pure fractions were collected the eluent was evaporated The residue was crystallized from 2,2'-oxybispropane The product was filtered off dried

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

Procedure: Ethyl-4-mercaptobenzoate was prepared by treating 4-mercaptobenzoic acid (1.50 g, 9.73 mmol) with ethanol (97 mL) in the presence of catalytic concentrated sulfuric acid under a nitrogen atmosphere. The reaction was heated at reflux for three hours. The volume of the reaction was reduced to 10 mL under reduced pressure and then partitioned between water (100 mL) and ethyl acetate (100 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL), and the combined organic solutions were washed with water (75 mL) and saturated aqueous sodium bicarbonate (2×75 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide an oil. The oil was dissolved in dichloromethane (100 mL), and the resulting solution was extracted with saturated aqueous sodium carbonate (3×100 mL). The combined extracts were washed with dichloromethane (3×50 mL) and then treated with concentrated hydrochloric acid to adjust to pH 7. The solution was then extracted with dichloromethane (3×100 mL), and the combined extracts were washed with water (50 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 1.23 g of ethyl-4-mercaptobenzoate as a colorless oil. Ethyl-4-mercaptobenzoate was prepared The reaction was heated at reflux for three hours partitioned between water (100 mL) and ethyl acetate (100 mL) The aqueous layer was extracted with ethyl acetate (3×100 mL) the combined organic solutions were washed with water (75 mL) and saturated aqueous sodium bicarbonate (2×75 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to provide an oil the resulting solution was extracted with saturated aqueous sodium carbonate (3×100 mL) The combined extracts were washed with dichloromethane (3×50 mL) treated with concentrated hydrochloric acid The solution was then extracted with dichloromethane (3×100 mL) the combined extracts were washed with water (50 mL) dried over magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a stirred solution of 5.6 parts of 1-(6-chloro-3-pyridazinyl)-4-piperidinepropanol, 4.2 parts of ethyl 4-mercaptobenzoate and 6 parts of triphenylposphine in 135 parts of tetrahydrofuran was added dropwise a solution of 4 parts of diethyl diazenedicarboxylate in 45 parts of tetrahydrofuran at 20° C. Upon complete addition, stirring was continued overnight at this temperature. The reaction mixture was evaporated and the residue was taken up in water. The product was ectracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (99:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried, yielding 1.3 parts (13.5%) of ethyl 4-[[3-[1-(6-chloro-3-pyridazinyl)-4-piperidinyl]propyl]thio]benzoate; mp. 96.3° C. (comp. 164). Upon complete addition The reaction mixture was evaporated The extract was dried filtered evaporated The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (99:1 by volume) as eluent The pure fractions were collected the eluent was evaporated The residue was crystallized from 2,2'-oxybispropane The product was filtered off dried