methyl 4-(chlorosulfonylmethyl)oxane-4-carboxylate

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

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

Procedure: Prepared according to the method for the preparation of 2-[4-(4-bromophenyl)piperazine-1-sulfonylmethyl]-3-methyl-butyric acid tert-buryl ester, from 1-(4-pyridin-3-yl-phenyl)piperazine (0.18 g) and 4-chlorosulfonylmethyl tetrahydropyran-4-carboxylic acid methyl ester (0.23 g), to yield the title compound as a white solid (0.19 g, 55%). Prepared

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

Procedure: 4-Chlorosulfonylmethyltetrahydropyran-4-carboxylic acid methyl ester (5.10 g) was added to a stirred suspension of 4-bromophenylpiperazine hydrochloride (5.51 g) and triethylamine (6.09 ml) in dichloromethane (120 ml), and the mixture was stirred at room temperature for 18 h. The dichloromethane was then removed under reduced pressure, and the residue redissolved in tetrahydrofuran (60 ml), methanol (30 ml) and water (15 ml), treated with lithium hydroxide monohydrate (4.15 g) and heated to reflux for 2 h. The organic solvents were removed in vacuo and the residue was diluted with 1 M sodium hydroxide (30 ml) and washed with diethyl ether (3×40 ml). The aqueous phase was then acidified to pH 4-5 with citric acid, forming a white precipitate, which was filtered, washed with water and dried to constant weight under vacuum at 40° C. to provide the title compound as a white solid (4.55 g, 51%). The dichloromethane was then removed under reduced pressure the residue redissolved in tetrahydrofuran (60 ml) methanol (30 ml) and water (15 ml), treated with lithium hydroxide monohydrate (4.15 g) heated to reflux for 2 h The organic solvents were removed in vacuo the residue was diluted with 1 M sodium hydroxide (30 ml) washed with diethyl ether (3×40 ml) forming a white precipitate, which was filtered washed with water dried to constant weight under vacuum at 40° C.

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: Prepared according to the method for the preparation of 2-[4-(4-bromophenyl)piperazine-1-sulfonylmethyl]-3-methyl-butyric acid ter-butyl ester, from 1-(4-pyridin-3-yl-phenyl)piperazine (0.18 g) and 4-chlorosulfonylmethyl tetrahydropyran-4-carboxylic acid methyl ester (0.23 g), to yield the title compound as a white solid (0.19 g, 55%). Prepared

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

Procedure: 4-Chlorosulfonylmethyltetrahydropyran-4-carboxylic acid methyl ester (5.10 g) was added to a stirred suspension of 4-bromophenylpiperazine hydrochloride (5.51 g) and triethylamine (6.09 ml) in dichloromethane (120 ml), and the mixture was stirred at room temperature for 18 h. The dichloromethane was then removed under reduced pressure, and the residue redissolved in tetrahydrofuran (60 ml), methanol (30 ml) and water (15 ml), treated with lithium hydroxide monohydrate (4.15 g) and heated to reflux for 2 h. The organic solvents were removed in vacuo and the residue was diluted with 1 M sodium hydroxide (30 ml) and washed with diethyl ether (3×40 ml). The aqueous phase was then acidified to pH 4-5 with citric acid, forming a white precipitate, which was filtered, washed with water and dried to constant weight under vacuum at 40° C. to provide the title compound as a white solid (4.55 g, 51%). The dichloromethane was then removed under reduced pressure the residue redissolved in tetrahydrofuran (60 ml) methanol (30 ml) and water (15 ml), treated with lithium hydroxide monohydrate (4.15 g) heated to reflux for 2 h The organic solvents were removed in vacuo the residue was diluted with 1 M sodium hydroxide (30 ml) washed with diethyl ether (3×40 ml) forming a white precipitate, which was filtered washed with water dried to constant weight under vacuum at 40° C.

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

Procedure: 4-Chlorosulfonylmethyl-tetrahydro-pyran-4-carboxylic acid methyl ester (520 mg) was added to a solution of 1,2,3,4-tetrahydrobenzo[4,5]thieno[2,3-c]pyridine hydrochloride (450 mg) and triethlyamine (1.0 ml) in tetrahydrofuran (20 ml). The mixture was stirred at room temperature for 18 h then water (5 ml), methanol (5 ml) and lithium hydroxide monohydrate (400 mg) were added and the reaction heated to reflux for 3 h. The mixture was evaporated under reduced pressure and the aqueous residue washed with diethyl ether (2×10 ml), acidified with 1M hydrochloric acid and the precipitate collected by filtration to give the title compound (200 mg, 25%) as a white solid. the reaction heated to reflux for 3 h The mixture was evaporated under reduced pressure the aqueous residue washed with diethyl ether (2×10 ml) the precipitate collected by filtration

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

Procedure: Prepared according to the method for the preparation of 2-[4-(4-bromophenyl)piperazine-1-sulfonylmethyl]-3-methyl-butyric acid tert-buryl ester, from 1-(4-pyridin-3-yl-phenyl)piperazine (0.18 g) and 4-chlorosulfonylmethyl tetrahydropyran-4-carboxylic acid methyl ester (0.23 g), to yield the title compound as a white solid (0.19 g, 55%). Prepared

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

Procedure: Prepared according to the method for the preparation of 2-[4-(4-bromophenyl)piperazine-1-sulfonylmethyl]-3-methyl-butyric acid tert-buryl ester, from 1-(4-pyridin-3-yl-phenyl)piperazine (0.18 g) and 4-chlorosulfonylmethyl tetrahydropyran-4-carboxylic acid methyl ester (0.23 g), to yield the title compound as a white solid (0.19 g, 55%). Prepared

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

Procedure: 4-Chlorosulfonylmethyltetrahydropyran-4-carboxylic acid methyl ester (5.10 g) was added to a stirred suspension of 4-bromophenylpiperazine hydrochloride (5.51 g) and triethylamine (6.09 ml) in dichloromethane (120 ml), and the mixture was stirred at room temperature for 18 h. The dichloromethane was then removed under reduced pressure, and the residue redissolved in tetrahydrofuran (60 ml), methanol (30 ml) and water (15 ml), treated with lithium hydroxide monohydrate (4.15 g) and heated to reflux for 2 h. The organic solvents were removed in vacuo and the residue was diluted with 1 M sodium hydroxide (30 ml) and washed with diethyl ether (3×40 ml). The aqueous phase was then acidified to pH 4-5 with citric acid, forming a white precipitate, which was filtered, washed with water and dried to constant weight under vacuum at 40° C. to provide the title compound as a white solid (4.55 g, 51%). The dichloromethane was then removed under reduced pressure the residue redissolved in tetrahydrofuran (60 ml) methanol (30 ml) and water (15 ml), treated with lithium hydroxide monohydrate (4.15 g) heated to reflux for 2 h The organic solvents were removed in vacuo the residue was diluted with 1 M sodium hydroxide (30 ml) washed with diethyl ether (3×40 ml) forming a white precipitate, which was filtered washed with water dried to constant weight under vacuum at 40° C.

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

Procedure: 4-Chlorosulfonylmethyl-tetrahydro-pyran-4-carboxylic acid methyl ester (520 mg) was added to a solution of 1,2,3,4-tetrahydrobenzo[4,5]thieno[2,3-c]pyridine hydrochloride (450 mg) and triethlyamine (1.0 ml) in tetrahydrofuran (20 ml). The mixture was stirred at room temperature for 18 h then water (5 ml), methanol (5 ml) and lithium hydroxide monohydrate (400 mg) were added and the reaction heated to reflux for 3 h. The mixture was evaporated under reduced pressure and the aqueous residue washed with diethyl ether (2×10 ml), acidified with 1M hydrochloric acid and the precipitate collected by filtration to give the title compound (200 mg, 25%) as a white solid. the reaction heated to reflux for 3 h The mixture was evaporated under reduced pressure the aqueous residue washed with diethyl ether (2×10 ml) the precipitate collected by filtration