2-propan-2-ylbenzenesulfonyl chloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 5.65 g of O-isopropyl P-ethyl(hydroxymethyl)phosphinate, (Example 22, Method B), 7.0 ml of triethylamine and 25 ml of methylene chloride was added dropwise over 45 minutes to a mixture of 50 ml of methylene chloride, 8.03 g of crude 2-methoxybenzenesulfonyl chloride, (Example 4), and 0.1 g of DMAP. The reaction temperature was kept between 20° C. and 27° C. during the addition. The reaction was allowed to stir at room temperature for four days and was then diluted with 80 ml of water and 100 ml of methylene chloride. The phases were separated, the organic phase dried with magnesium sulfate, filtered and concentrated to yield 7.8 g of the crude product as a brown oil. Phosphorus NMR indicated two products in a 1:1 ratio. The crude product was dissolved in 35 ml of acetic acid and 12 ml of 30% hydrogen peroxide solution was added. After stirring for 10 minutes, the reaction temperature was slowly increased to 90° C. for 2.5 hours. The reaction was allowed to cool to room temperature and stand overnight and was then poured onto 100 g of ice and the mixture diluted with 100 ml of water. After the ice had melted, the aqueous mixture was extracted with 200 ml of ethyl acetate, the phases separated, the organic phase washed with 100 ml of saturated sodium bicarbonate solution, dried with magnesium sulfate, filtered, and concentrated to yield the crude product as an oil. The oil was dissolved in 4 ml of methylene chloride and flash chromatographed on Merck silica gel (230-400 mesh) using blends of hexanes and ethyl acetate ranging from 30/70 to 10/90 hexanes and ethyl acetate, respectively. Similar fractions were combined and concentrated to yield 0.5 g of the desired product. The reaction temperature was kept between 20° C. and 27° C. during the addition The phases were separated the organic phase dried with magnesium sulfate filtered concentrated to yield 7.8 g of the crude product as a brown oil After stirring for 10 minutes the reaction temperature was slowly increased to 90° C. for 2.5 hours to cool to room temperature stand overnight the aqueous mixture was extracted with 200 ml of ethyl acetate the phases separated the organic phase washed with 100 ml of saturated sodium bicarbonate solution dried with magnesium sulfate filtered concentrated to yield the crude product as an oil flash chromatographed on Merck silica gel (230-400 mesh) concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-methoxybenzenesulfonyl chloride and 5-chloro-2-methoxybenzenesulfonyl chloride, which results from ring chlorination, was prepared from 2-methoxythiophenol. results from ring chlorination

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6,8-Dichloro-2-propyl-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]isoindol-7-yl-amine (100 mg, 0.33 mmol) and polystyrene-bound DMAP (4-(N,N-dimethylamino)pyridine) (loading 1.06 mmol/g, 32 mg) were treated with tetrahydrofuran (10 ml). Subsequently isopropylphenylsulfonyl chloride (73 mg, 0.33 mmol) was added and stirred for 5 hours at 150° C. in the microwave (CEM). Another portion of isopropylphenylsulfonyl chloride and polystyrene-bound DMAP was added and stirring continued for 7 hours at 160° C. in the microwave. The solvent was evaporated under reduced pressure, the residue treated with water (30 ml) and twice extracted with ethyl acetate (2×30 ml). The organic layer was dried over magnesium sulfate, filtered, and the solvent evaporated under reduced pressure to give an oil (470 mg). The crude product was purified via HPLC chromatography. Fractions containing the product were combined and the solvent evaporated. The residue was converted into the hydrochloride salt (4 mg, 2%). stirring continued for 7 hours at 160° C. in the microwave The solvent was evaporated under reduced pressure the residue treated with water (30 ml) twice extracted with ethyl acetate (2×30 ml) The organic layer was dried over magnesium sulfate filtered the solvent evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 5.65 g of O-isopropyl P-ethyl(hydroxymethyl)phosphinate, (Example 22, Method B), 7.0 ml of triethylamine and 25 ml of methylene chloride was added dropwise over 45 minutes to a mixture of 50 ml of methylene chloride, 8.03 g of crude 2-methoxybenzenesulfonyl chloride, (Example 4), and 0.1 g of DMAP. The reaction temperature was kept between 20° C. and 27° C. during the addition. The reaction was allowed to stir at room temperature for four days and was then diluted with 80 ml of water and 100 ml of methylene chloride. The phases were separated, the organic phase dried with magnesium sulfate, filtered and concentrated to yield 7.8 g of the crude product as a brown oil. Phosphorus NMR indicated two products in a 1:1 ratio. The crude product was dissolved in 35 ml of acetic acid and 12 ml of 30% hydrogen peroxide solution was added. After stirring for 10 minutes, the reaction temperature was slowly increased to 90° C. for 2.5 hours. The reaction was allowed to cool to room temperature and stand overnight and was then poured onto 100 g of ice and the mixture diluted with 100 ml of water. After the ice had melted, the aqueous mixture was extracted with 200 ml of ethyl acetate, the phases separated, the organic phase washed with 100 ml of saturated sodium bicarbonate solution, dried with magnesium sulfate, filtered, and concentrated to yield the crude product as an oil. The oil was dissolved in 4 ml of methylene chloride and flash chromatographed on Merck silica gel (230-400 mesh) using blends of hexanes and ethyl acetate ranging from 30/70 to 10/90 hexanes and ethyl acetate, respectively. Similar fractions were combined and concentrated to yield 0.5 g of the desired product. The reaction temperature was kept between 20° C. and 27° C. during the addition The phases were separated the organic phase dried with magnesium sulfate filtered concentrated to yield 7.8 g of the crude product as a brown oil After stirring for 10 minutes the reaction temperature was slowly increased to 90° C. for 2.5 hours to cool to room temperature stand overnight the aqueous mixture was extracted with 200 ml of ethyl acetate the phases separated the organic phase washed with 100 ml of saturated sodium bicarbonate solution dried with magnesium sulfate filtered concentrated to yield the crude product as an oil flash chromatographed on Merck silica gel (230-400 mesh) concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 5.65 g of O-isopropyl P-ethyl(hydroxymethyl)phosphinate, (Example 22, Method B), 7.0 ml of triethylamine and 25 ml of methylene chloride was added dropwise over 45 minutes to a mixture of 50 ml of methylene chloride, 8.03 g of crude 2-methoxybenzenesulfonyl chloride, (Example 4), and 0.1 g of DMAP. The reaction temperature was kept between 20° C. and 27° C. during the addition. The reaction was allowed to stir at room temperature for four days and was then diluted with 80 ml of water and 100 ml of methylene chloride. The phases were separated, the organic phase dried with magnesium sulfate, filtered and concentrated to yield 7.8 g of the crude product as a brown oil. Phosphorus NMR indicated two products in a 1:1 ratio. The crude product was dissolved in 35 ml of acetic acid and 12 ml of 30% hydrogen peroxide solution was added. After stirring for 10 minutes, the reaction temperature was slowly increased to 90° C. for 2.5 hours. The reaction was allowed to cool to room temperature and stand overnight and was then poured onto 100 g of ice and the mixture diluted with 100 ml of water. After the ice had melted, the aqueous mixture was extracted with 200 ml of ethyl acetate, the phases separated, the organic phase washed with 100 ml of saturated sodium bicarbonate solution, dried with magnesium sulfate, filtered, and concentrated to yield the crude product as an oil. The oil was dissolved in 4 ml of methylene chloride and flash chromatographed on Merck silica gel (230-400 mesh) using blends of hexanes and ethyl acetate ranging from 30/70 to 10/90 hexanes and ethyl acetate, respectively. Similar fractions were combined and concentrated to yield 0.5 g of the desired product. The reaction temperature was kept between 20° C. and 27° C. during the addition The phases were separated the organic phase dried with magnesium sulfate filtered concentrated to yield 7.8 g of the crude product as a brown oil After stirring for 10 minutes the reaction temperature was slowly increased to 90° C. for 2.5 hours to cool to room temperature stand overnight the aqueous mixture was extracted with 200 ml of ethyl acetate the phases separated the organic phase washed with 100 ml of saturated sodium bicarbonate solution dried with magnesium sulfate filtered concentrated to yield the crude product as an oil flash chromatographed on Merck silica gel (230-400 mesh) concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-methoxybenzenesulfonyl chloride and 5-chloro-2-methoxybenzenesulfonyl chloride, which results from ring chlorination, was prepared from 2-methoxythiophenol. results from ring chlorination

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-methoxybenzenesulfonyl chloride and 5-chloro-2-methoxybenzenesulfonyl chloride, which results from ring chlorination, was prepared from 2-methoxythiophenol. results from ring chlorination

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 27 g of 2-isopropylbenzenesulfonyl chloride and 22 g of KF are stirred in 75 ml of dioxane and 20 ml of water at 45° C. for 27 h and at RT for 45 h. 800 ml of water are then added, and the mixture is extracted with 3×300 ml of EA. The combined organic phases are dried over Na2SO4 and the solvent is removed in vacuo. 24 g of a colorless oil are obtained. the mixture is extracted with 3×300 ml of EA The combined organic phases are dried over Na2SO4 the solvent is removed in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 5.65 g of O-isopropyl P-ethyl(hydroxymethyl)-phosphinate, (Example 22, Method B), 7.0 ml of triethylamine and 25 ml of methylene chloride was added dropwise over 45 minutes to a mixture of 50 ml of methylene chloride, 8.03 g of crude 2-methoxybenzenesulfonyl chloride, (Example 4), and 0.1 g of DMAP. The reaction temperature was kept between 20° C. and 27° C. during the addition. The reaction was allowed to stir at room temperature for four days and was then diluted with 80 ml of water and 100 ml of methylene chloride. The phases were separated, the organic phase dried with magnesium sulfate, filtered and concentrated to yield 7.8 g of the crude product as a brown oil. Phosphorus NMR indicated two products in a 1:1 ratio. The crude product was dissolved in 35 ml of acetic acid and 12 ml of 30% hydrogen peroxide solution was added. After stirring for 10 minutes, the reaction temperature was slowly increased to 90° C. for 2.5 hours. The reaction was allowed to cool to room temperature and stand overnight and was then poured onto 100 g of ice and the mixture diluted with 100 ml of water. After the ice had melted, the aqueous mixture was extracted with 200 ml of ethyl acetate, the phases separated, the organic phase washed with 100 ml of saturated sodium bicarbonate solution, dried with magnesium sulfate, filtered, and concentrated to yield the crude product as an oil. The oil was dissolved in 4 ml of methylene chloride and flash chromatographed on Merck silica gel (230-400 mesh) using blends of hexanes and ethyl acetate ranging from 30/70 to 10/90 hexanes and ethyl acetate, respectively. Similar fractions were combined and concentrated to yield 0.5 g of the desired product. The reaction temperature was kept between 20° C. and 27° C. during the addition The phases were separated the organic phase dried with magnesium sulfate filtered concentrated to yield 7.8 g of the crude product as a brown oil After stirring for 10 minutes the reaction temperature was slowly increased to 90° C. for 2.5 hours to cool to room temperature stand overnight the aqueous mixture was extracted with 200 ml of ethyl acetate the phases separated the organic phase washed with 100 ml of saturated sodium bicarbonate solution dried with magnesium sulfate filtered concentrated to yield the crude product as an oil flash chromatographed on Merck silica gel (230-400 mesh) concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-methoxybenzenesulfonyl chloride and 5-chloro-2-methoxybenzenesulfonyl chloride, which results from ring chlorination, was prepared from 2-methoxythiophenol. results from ring chlorination

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6,8-Dichloro-2-propyl-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]isoindol-7-yl-amine (100 mg, 0.33 mmol) and polystyrene-bound DMAP (4-(N,N-dimethylamino)pyridine) (loading 1.06 mmol/g, 32 mg) were treated with tetrahydrofuran (10 ml). Subsequently isopropylphenylsulfonyl chloride (73 mg, 0.33 mmol) was added and stirred for 5 hours at 150° C. in the microwave (CEM). Another portion of isopropylphenylsulfonyl chloride and polystyrene-bound DMAP was added and stirring continued for 7 hours at 160° C. in the microwave. The solvent was evaporated under reduced pressure, the residue treated with water (30 ml) and twice extracted with ethyl acetate (2×30 ml). The organic layer was dried over magnesium sulfate, filtered, and the solvent evaporated under reduced pressure to give an oil (470 mg). The crude product was purified via HPLC chromatography. Fractions containing the product were combined and the solvent evaporated. The residue was converted into the hydrochloride salt (4 mg, 2%). stirring continued for 7 hours at 160° C. in the microwave The solvent was evaporated under reduced pressure the residue treated with water (30 ml) twice extracted with ethyl acetate (2×30 ml) The organic layer was dried over magnesium sulfate filtered the solvent evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 5.65 g of O-isopropyl P-ethyl(hydroxymethyl)phosphinate, (Example 22, Method B), 7.0 ml of triethylamine and 25 ml of methylene chloride was added dropwise over 45 minutes to a mixture of 50 ml of methylene chloride, 8.03 g of crude 2-methoxybenzenesulfonyl chloride, (Example 4), and 0.1 g of DMAP. The reaction temperature was kept between 20° C. and 27° C. during the addition. The reaction was allowed to stir at room temperature for four days and was then diluted with 80 ml of water and 100 ml of methylene chloride. The phases were separated, the organic phase dried with magnesium sulfate, filtered and concentrated to yield 7.8 g of the crude product as a brown oil. Phosphorus NMR indicated two products in a 1:1 ratio. The crude product was dissolved in 35 ml of acetic acid and 12 ml of 30% hydrogen peroxide solution was added. After stirring for 10 minutes, the reaction temperature was slowly increased to 90° C. for 2.5 hours. The reaction was allowed to cool to room temperature and stand overnight and was then poured onto 100 g of ice and the mixture diluted with 100 ml of water. After the ice had melted, the aqueous mixture was extracted with 200 ml of ethyl acetate, the phases separated, the organic phase washed with 100 ml of saturated sodium bicarbonate solution, dried with magnesium sulfate, filtered, and concentrated to yield the crude product as an oil. The oil was dissolved in 4 ml of methylene chloride and flash chromatographed on Merck silica gel (230-400 mesh) using blends of hexanes and ethyl acetate ranging from 30/70 to 10/90 hexanes and ethyl acetate, respectively. Similar fractions were combined and concentrated to yield 0.5 g of the desired product. The reaction temperature was kept between 20° C. and 27° C. during the addition The phases were separated the organic phase dried with magnesium sulfate filtered concentrated to yield 7.8 g of the crude product as a brown oil After stirring for 10 minutes the reaction temperature was slowly increased to 90° C. for 2.5 hours to cool to room temperature stand overnight the aqueous mixture was extracted with 200 ml of ethyl acetate the phases separated the organic phase washed with 100 ml of saturated sodium bicarbonate solution dried with magnesium sulfate filtered concentrated to yield the crude product as an oil flash chromatographed on Merck silica gel (230-400 mesh) concentrated