1-(benzenesulfonyl)propan-2-one

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

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.9 g of 3-aminocrotonic acid methyl ester and 13.9 g of phenylsulphonylacetone are added to 9.1 g of o-nitrobenz- aldehyde dissolved in 50 ml of hexamethylphosphoric acid triamide. The mixture is then stirred for 10 hours under nitrogen at a bath temperature of 110° C. The mixture is cooled and dissolved in 400 ml of ethyl acetate and the solution is washed with a mixture of 400 ml of water, 60 ml of methanol and 60 ml of saturated sodium chloride solution. The aqueous phase is separated off and the organic phase is washed with 3 times 100 ml of water, with twice 100 ml of 1 N hydrochloric acid solution, with twice 60 ml of saturated sodium bicarbonate solution and once with 60 ml of 2 N sodium carbonate solution. The ethyl acetate phase is dried over sodium sulphate and evaporated. The residue is chromatographed on silica gel using a mixture of toluene and ethyl acetate (7:3) as the eluant. The eluate is evaporated and crystallised from methanol. In this way, 2,6dimethyl-3-carbomethoxy-4-(2-nitrophenyl)-5- phenylsulphonyl-1,4-dihydropyridine, of melting point 203° C, is obtained. The mixture is cooled the solution is washed with a mixture of 400 ml of water, 60 ml of methanol and 60 ml of saturated sodium chloride solution The aqueous phase is separated off the organic phase is washed with 3 times 100 ml of water, with twice 100 ml of 1 N hydrochloric acid solution, with twice 60 ml of saturated sodium bicarbonate solution and once with 60 ml of 2 N sodium carbonate solution The ethyl acetate phase is dried over sodium sulphate evaporated The residue is chromatographed on silica gel using a mixture of toluene and ethyl acetate (7:3) as the eluant The eluate is evaporated crystallised from methanol

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, sodium hydride (6.41 g, 0.267 mol) and THF (125 ml) were combined and the suspension was cooled to -15° C. A THF solution (150 ml) of (phenylsulfonyl)acetone (50 g, 0.253 mol) was added to the suspension in a dropwise fashion over an hour. The resultant mixture was stirred for an additional 20 minutes at -15° C. Allyl bromoacetate (47.5 g, 0.265 mol) dissolved in THF (100 ml) was added in a dropwise fashion to the mixture over a period of 30 minutes while maintaining the temperature of the solution below 0° C. The resultant solution was stirred at -5° C. for 15 minutes, allowed to warm to room temperature over a period of an hour, and stirred overnight at room temperature. The reaction solution was poured into saturated aqueous ammonium chloride solution (800 ml) and chloroform (500 ml) and the aqueous layer was separated and extracted with chloroform (2X, 200 ml). The chloroform layers were combined and washed with saturated aqueous sodium chloride (1X, 350 ml), dried over sodium sulfate, filtered and concentrated in vacuo to an oil. The oil was crystallized from a mixture of ethyl acetate and hexane. The collected solid was washed with cold 1:3 ethyl acetate: hexane and dried in vacuo, yielding 52.9 g of the allyl 3-(phenylsulfonyl)-4-oxopentanoate: n.m.r. (90 MHz, CDCl3): δ 2.51 (s, 3), 2.97 (n, 2,), 4.51 (dm, 2, J=6), 4.65 (m, 1), 5.1-5.19 (m,2), 5.58-6.00 (m, 1), 7.4-7.8 (m, 5); m.p. 62-64° C. was added in a dropwise fashion to the mixture over a period of 30 minutes while maintaining the temperature of the solution below 0° C to warm to room temperature over a period of an hour the aqueous layer was separated extracted with chloroform (2X, 200 ml) washed with saturated aqueous sodium chloride (1X, 350 ml) dried over sodium sulfate filtered concentrated in vacuo to an oil The oil was crystallized from a mixture of ethyl acetate and hexane The collected solid was washed with cold 1:3 ethyl acetate hexane and dried in vacuo

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium benzenesulfinate (50 g, 304.6 mmol) was dissolved in water (200 ml). A dioxane solution (200 ml) of chloroacetone (29.6 g, 319.9 mmol) was added and the solution was stirred and heated to 50° C. for 22 hours then cooled to approximately 25° C. The solution was extracted with methylene chloride (2X, 250 ml), the methylene chloride layers were combined and washed with saturated aqueous sodium bicarbonate solution (1X, 250 ml) and water (1X, 250 ml) then the aqueous wash solutions were combined and extracted with methylene chloride (2X, 100 ml). All of the methylene chloride layers were combined and washed with saturated aqueous sodium chloride solution (1X, 150 ml), dried over sodium sulfate, filtered and concentrated in vacuo to a solid. The solid was dissolved in diethyl ether (800 ml) with gentle heating and then the solution was stirred and allowed to cool to room temperature. The solution was slowly cooled to 0° C. with stirring, causing the product to crystallize. The resulting crystals were collected by filtration, washed with cold diethyl ether, and dried in vacuo at 35° C. for 4 hours to yield 36.43 g of (phenylsulfonyl)acetone. The filtrate was concentrated to approximately one-eighth of its volume in vacuo and was gradually cooled below room temperature to induce crystallization, then stirred overnight at room temperature. The resulting crystals were collected by filtration, washed with cold diethyl ether, and dried in vacuo at 35° C. for 8 hours to yield an additional 14 g of the (phenylsulfonyl)acetone: n.m.r. (90 MHz, CDCl3): δ 2.39 (s, 3), 4.17 (s, 2), 7.55-7.95 (m, 5); m.p. 56°-58° C. then cooled to approximately 25° C The solution was extracted with methylene chloride (2X, 250 ml) washed with saturated aqueous sodium bicarbonate solution (1X, 250 ml) and water (1X, 250 ml) extracted with methylene chloride (2X, 100 ml) washed with saturated aqueous sodium chloride solution (1X, 150 ml) dried over sodium sulfate filtered concentrated in vacuo to a solid The solid was dissolved in diethyl ether (800 ml) with gentle heating the solution was stirred to cool to room temperature The solution was slowly cooled to 0° C. with stirring to crystallize The resulting crystals were collected by filtration washed with cold diethyl ether dried in vacuo at 35° C. for 4 hours

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium benzenesulfinate (50 g, 304.6 mmol) was dissolved in water (200 ml). A dioxane solution (200 ml) of chloroacetone (29.6 g, 319.9 mmol) was added and the solution was stirred and heated to 50° C. for 22 hours then cooled to approximately 25° C. The solution was extracted with methylene chloride (2X, 250 ml), the methylene chloride layers were combined and washed with saturated aqueous sodium bicarbonate solution (1X, 250 ml) and water (1X, 250 ml) then the aqueous wash solutions were combined and extracted with methylene chloride (2X, 100 ml). All of the methylene chloride layers were combined and washed with saturated aqueous sodium chloride solution (1X, 150 ml), dried over sodium sulfate, filtered and concentrated in vacuo to a solid. The solid was dissolved in diethyl ether (800 ml) with gentle heating and then the solution was stirred and allowed to cool to room temperature. The solution was slowly cooled to 0° C. with stirring, causing the product to crystallize. The resulting crystals were collected by filtration, washed with cold diethyl ether, and dried in vacuo at 35° C. for 4 hours to yield 36.43 g of (phenylsulfonyl)acetone. The filtrate was concentrated to approximately one-eighth of its volume in vacuo and was gradually cooled below room temperature to induce crystallization, then stirred overnight at room temperature. The resulting crystals were collected by filtration, washed with cold diethyl ether, and dried in vacuo at 35° C. for 8 hours to yield an additional 14 g of the (phenylsulfonyl)acetone: n.m.r. (90 MHz, CDCl3): δ 2.39 (s, 3), 4.17 (s, 2), 7.55-7.95 (m, 5); m.p. 56°-58° C. then cooled to approximately 25° C The solution was extracted with methylene chloride (2X, 250 ml) washed with saturated aqueous sodium bicarbonate solution (1X, 250 ml) and water (1X, 250 ml) extracted with methylene chloride (2X, 100 ml) washed with saturated aqueous sodium chloride solution (1X, 150 ml) dried over sodium sulfate filtered concentrated in vacuo to a solid The solid was dissolved in diethyl ether (800 ml) with gentle heating the solution was stirred to cool to room temperature The solution was slowly cooled to 0° C. with stirring to crystallize The resulting crystals were collected by filtration washed with cold diethyl ether dried in vacuo at 35° C. for 4 hours

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

Procedure: To a stirred suspension of 100.0 g (0.504 mole) phenylsulfonylacetone in 500 ml carbon tetrachloride, 80 g [25.7 ml (0.5 mole)] bromine dissolved in 75 g carbon tetrachloride were added dropwise. The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was filtered, and the precipitate was washed with hexane to give 139.8 g of the above-identified product. were added dropwise The reaction mixture was filtered the precipitate was washed with hexane

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

Procedure: To a stirred suspension of 100.0 g (0.504 mole) phenylsulfonylacetone in 500 ml carbon tetrachloride, 80 g [25.7 ml (0.5 mole)] bromine dissolved in 75 g carbon tetrachloride were added dropwise. The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was filtered, and the precipitate was washed with hexane to give 139.8 g of the above-identified product. were added dropwise The reaction mixture was filtered the precipitate was washed with hexane

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.9 g of 3-aminocrotonic acid methyl ester and 13.9 g of phenylsulphonylacetone are added to 9.1 g of o-nitrobenz- aldehyde dissolved in 50 ml of hexamethylphosphoric acid triamide. The mixture is then stirred for 10 hours under nitrogen at a bath temperature of 110° C. The mixture is cooled and dissolved in 400 ml of ethyl acetate and the solution is washed with a mixture of 400 ml of water, 60 ml of methanol and 60 ml of saturated sodium chloride solution. The aqueous phase is separated off and the organic phase is washed with 3 times 100 ml of water, with twice 100 ml of 1 N hydrochloric acid solution, with twice 60 ml of saturated sodium bicarbonate solution and once with 60 ml of 2 N sodium carbonate solution. The ethyl acetate phase is dried over sodium sulphate and evaporated. The residue is chromatographed on silica gel using a mixture of toluene and ethyl acetate (7:3) as the eluant. The eluate is evaporated and crystallised from methanol. In this way, 2,6dimethyl-3-carbomethoxy-4-(2-nitrophenyl)-5- phenylsulphonyl-1,4-dihydropyridine, of melting point 203° C, is obtained. The mixture is cooled the solution is washed with a mixture of 400 ml of water, 60 ml of methanol and 60 ml of saturated sodium chloride solution The aqueous phase is separated off the organic phase is washed with 3 times 100 ml of water, with twice 100 ml of 1 N hydrochloric acid solution, with twice 60 ml of saturated sodium bicarbonate solution and once with 60 ml of 2 N sodium carbonate solution The ethyl acetate phase is dried over sodium sulphate evaporated The residue is chromatographed on silica gel using a mixture of toluene and ethyl acetate (7:3) as the eluant The eluate is evaporated crystallised from methanol

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.9 g of 3-aminocrotonic acid methyl ester and 13.9 g of phenylsulphonylacetone are added to 9.1 g of o-nitrobenz- aldehyde dissolved in 50 ml of hexamethylphosphoric acid triamide. The mixture is then stirred for 10 hours under nitrogen at a bath temperature of 110° C. The mixture is cooled and dissolved in 400 ml of ethyl acetate and the solution is washed with a mixture of 400 ml of water, 60 ml of methanol and 60 ml of saturated sodium chloride solution. The aqueous phase is separated off and the organic phase is washed with 3 times 100 ml of water, with twice 100 ml of 1 N hydrochloric acid solution, with twice 60 ml of saturated sodium bicarbonate solution and once with 60 ml of 2 N sodium carbonate solution. The ethyl acetate phase is dried over sodium sulphate and evaporated. The residue is chromatographed on silica gel using a mixture of toluene and ethyl acetate (7:3) as the eluant. The eluate is evaporated and crystallised from methanol. In this way, 2,6dimethyl-3-carbomethoxy-4-(2-nitrophenyl)-5- phenylsulphonyl-1,4-dihydropyridine, of melting point 203° C, is obtained. The mixture is cooled the solution is washed with a mixture of 400 ml of water, 60 ml of methanol and 60 ml of saturated sodium chloride solution The aqueous phase is separated off the organic phase is washed with 3 times 100 ml of water, with twice 100 ml of 1 N hydrochloric acid solution, with twice 60 ml of saturated sodium bicarbonate solution and once with 60 ml of 2 N sodium carbonate solution The ethyl acetate phase is dried over sodium sulphate evaporated The residue is chromatographed on silica gel using a mixture of toluene and ethyl acetate (7:3) as the eluant The eluate is evaporated crystallised from methanol

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

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, sodium hydride (6.41 g, 0.267 mol) and THF (125 ml) were combined and the suspension was cooled to -15° C. A THF solution (150 ml) of (phenylsulfonyl)acetone (50 g, 0.253 mol) was added to the suspension in a dropwise fashion over an hour. The resultant mixture was stirred for an additional 20 minutes at -15° C. Allyl bromoacetate (47.5 g, 0.265 mol) dissolved in THF (100 ml) was added in a dropwise fashion to the mixture over a period of 30 minutes while maintaining the temperature of the solution below 0° C. The resultant solution was stirred at -5° C. for 15 minutes, allowed to warm to room temperature over a period of an hour, and stirred overnight at room temperature. The reaction solution was poured into saturated aqueous ammonium chloride solution (800 ml) and chloroform (500 ml) and the aqueous layer was separated and extracted with chloroform (2X, 200 ml). The chloroform layers were combined and washed with saturated aqueous sodium chloride (1X, 350 ml), dried over sodium sulfate, filtered and concentrated in vacuo to an oil. The oil was crystallized from a mixture of ethyl acetate and hexane. The collected solid was washed with cold 1:3 ethyl acetate:hexane and dried in vacuo, yielding 52.9 g of the allyl 3-(phenylsulfonyl)-4-oxopentanoate: n.m.r. (90 MHz, CDCl3): δ 2.51 (s, 3), 2.97 (n, 2,), 4.51 (dm, 2, J=6), 4.65 (m, 1), 5.1-5.19 (m,2), 5.58-6.00 (m, 1), 7.4-7.8 (m, 5); m.p. 62-64° C. was added in a dropwise fashion to the mixture over a period of 30 minutes while maintaining the temperature of the solution below 0° C to warm to room temperature over a period of an hour the aqueous layer was separated extracted with chloroform (2X, 200 ml) washed with saturated aqueous sodium chloride (1X, 350 ml) dried over sodium sulfate filtered concentrated in vacuo to an oil The oil was crystallized from a mixture of ethyl acetate and hexane The collected solid was washed with cold 1:3 ethyl acetate hexane and dried in vacuo

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium benzenesulfinate (50 g, 304.6 mmol) was dissolved in water (200 ml). A dioxane solution (200 ml) of chloroacetone (29.6 g, 319.9 mmol) was added and the solution was stirred and heated to 50° C. for 22 hours then cooled to approximately 25° C. The solution was extracted with methylene chloride (2X, 250 ml), the methylene chloride layers were combined and washed with saturated aqueous sodium bicarbonate solution (1X, 250 ml) and water (1X, 250 ml) then the aqueous wash solutions were combined and extracted with methylene chloride (2X, 100 ml). All of the methylene chloride layers were combined and washed with saturated aqueous sodium chloride solution (1X, 150 ml), dried over sodium sulfate, filtered and concentrated in vacuo to a solid. The solid was dissolved in diethyl ether (800 ml) with gentle heating and then the solution was stirred and allowed to cool to room temperature. The solution was slowly cooled to 0° C. with stirring, causing the product to crystallize. The resulting crystals were collected by filtration, washed with cold diethyl ether, and dried in vacuo at 35° C. for 4 hours to yield 36.43 g of (phenylsulfonyl)acetone. The filtrate was concentrated to approximately one-eighth of its volume in vacuo and was gradually cooled below room temperature to induce crystallization, then stirred overnight at room temperature. The resulting crystals were collected by filtration, washed with cold diethyl ether, and dried in vacuo at 35° C. for 8 hours to yield an additional 14 g of the (phenylsulfonyl)acetone: n.m.r. (90 MHz, CDCl3): δ 2.39 (s, 3), 4.17 (s, 2), 7.55-7.95 (m, 5); m.p. 56°-58° C. then cooled to approximately 25° C The solution was extracted with methylene chloride (2X, 250 ml) washed with saturated aqueous sodium bicarbonate solution (1X, 250 ml) and water (1X, 250 ml) extracted with methylene chloride (2X, 100 ml) washed with saturated aqueous sodium chloride solution (1X, 150 ml) dried over sodium sulfate filtered concentrated in vacuo to a solid The solid was dissolved in diethyl ether (800 ml) with gentle heating the solution was stirred to cool to room temperature The solution was slowly cooled to 0° C. with stirring to crystallize The resulting crystals were collected by filtration washed with cold diethyl ether dried in vacuo at 35° C. for 4 hours