piperazine-1-sulfonamide

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

Procedure: (S)-Epichlorohydrin (48.0 mL, 0.612 mol) was added to a stirred solution of piperazine sulfonamide (87.3 g, 0.532 mol) in ethanol (1.33 L) at room temperature. The reaction mixture was stirred for 18 h and the white solid precipitate which formed was collected by filtration and washed with ethanol to afford the title intermediate (107.76 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). the white solid precipitate which formed was collected by filtration washed with ethanol

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

Procedure: (S)-Epichlorohydrin (48.0 mL, 0.612 mol) was added to a stirred solution of piperazine sulfonamide (87.3 g, 0.532 mol) in ethanol (1.33 L) at room temperature. The reaction mixture was stirred for 18 h and the white solid precipitate which formed was collected by filtration and washed with ethanol to afford the title intermediate (107.76 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). the white solid precipitate which formed was collected by filtration washed with ethanol

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

Procedure: (R)-Epichlorohydrin (3.10 mL, 39.5 mmol) was added to a stirred solution of piperazine sulfonamide. TFA (10.0 g, 35.9 mmol) and diisopropylethylamine (6.26 mL, 35.9 mmol) in ethanol (150 mL) at room temperature. The reaction mixture was stirred for 18 h and a further amount of (R)-epichlorohydrin was added (0.28 mL, 3.6 mmol) and stirred for an additional 3 h. The reaction mixture was concentrated in vacuo and the white solid was suspended in ethanol (150 mL) and stirred for 2 days. The solid was collected by filtration and washed with cold ethanol to afford the title compound (5.69 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). at room temperature stirred for an additional 3 h The reaction mixture was concentrated in vacuo stirred for 2 days The solid was collected by filtration washed with cold ethanol

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

Procedure: (S)-Epichlorohydrin (48.0 mL, 0.612 mol) was added to a stirred solution of piperazine sulfonamide (87.3 g, 0.532 mol) in ethanol (1.33 L) at room temperature. The reaction mixture was stirred for 18 h and the white solid precipitate which formed was collected by filtration and washed with ethanol to afford the title intermediate (107.76 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). the white solid precipitate which formed was collected by filtration washed with ethanol

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

Procedure: (R)-Epichlorohydrin (3.10 mL, 39.5 mmol) was added to a stirred solution of piperazine sulfonamide.TFA (10.0 g, 35.9 mmol) and diisopropylethylamine (6.26 mL, 35.9 mmol) in ethanol (150 mL) at room temperature. The reaction mixture was stirred for 18 h and a further amount of (R)-epichlorohydrin was added (0.28 mL, 3.6 mmol) and stirred for an additional 3 h. The reaction mixture was concentrated in vacuo and the white solid was suspended in ethanol (150 mL) and stirred for 2 days. The solid was collected by filtration and washed with cold ethanol to afford the title compound (5.69 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). at room temperature stirred for an additional 3 h The reaction mixture was concentrated in vacuo stirred for 2 days The solid was collected by filtration washed with cold ethanol

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

Procedure: (S)-Epichlorohydrin (48.0 mL, 0.612 mol) was added to a stirred solution of piperazine sulfonamide (87.3 g, 0.532 mol) in ethanol (1.33 L) at room temperature. The reaction mixture was stirred for 18 h and the white solid precipitate which formed was collected by filtration and washed with ethanol to afford the title intermediate (107.76 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). the white solid precipitate which formed was collected by filtration washed with ethanol

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

Procedure: (R)-Epichlorohydrin (3.10 mL, 39.5 mmol) was added to a stirred solution of piperazine sulfonamide.TFA (10.0 g, 35.9 mmol) and diisopropylethylamine (6.26 mL, 35.9 mmol) in ethanol (150 mL) at room temperature. The reaction mixture was stirred for 18 h and a further amount of (R)-epichlorohydrin was added (0.28 mL, 3.6 mmol) and stirred for an additional 3 h. The reaction mixture was concentrated in vacuo and the white solid was suspended in ethanol (150 mL) and stirred for 2 days. The solid was collected by filtration and washed with cold ethanol to afford the title compound (5.69 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). at room temperature stirred for an additional 3 h The reaction mixture was concentrated in vacuo stirred for 2 days The solid was collected by filtration washed with cold ethanol

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

Procedure: A solution of 1-diphenylmethyl-3-methanesulphonyloxyazetidine (see Preparation 54) (4.8 g, 15.1 mmol) and 1-aminosulphonylpiperazine (see Example 123(f)) (5 g) in acetonitrile (50 ml) was heated under reflux for 4 hours. The reaction was cooled and the solid filtered off and washed with acetonitrile (50 ml). The filtrate was concentrated under reduced pressure and the residue slurried in hot toluene (50 ml), cooled, the solid filtered off and washed with toluene (50 ml). The product was then further purified by slurrying in hot ethyl acetate (3 ml), cooling and filtering to give the title compound (0.47 g). under reflux for 4 hours The reaction was cooled the solid filtered off washed with acetonitrile (50 ml) The filtrate was concentrated under reduced pressure the residue slurried in hot toluene (50 ml), cooled the solid filtered off washed with toluene (50 ml) The product was then further purified cooling filtering

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

Procedure: (S)-Epichlorohydrin (48.0 mL, 0.612 mol) was added to a stirred solution of piperazine sulfonamide (87.3 g, 0.532 mol) in ethanol (1.33 L) at room temperature. The reaction mixture was stirred for 18 h and the white solid precipitate which formed was collected by filtration and washed with ethanol to afford the title intermediate (107.76 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). the white solid precipitate which formed was collected by filtration washed with ethanol

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

Procedure: (R)-Epichlorohydrin (3.10 mL, 39.5 mmol) was added to a stirred solution of piperazine sulfonamide. TFA (10.0 g, 35.9 mmol) and diisopropylethylamine (6.26 mL, 35.9 mmol) in ethanol (150 mL) at room temperature. The reaction mixture was stirred for 18 h and a further amount of (R)-epichlorohydrin was added (0.28 mL, 3.6 mmol) and stirred for an additional 3 h. The reaction mixture was concentrated in vacuo and the white solid was suspended in ethanol (150 mL) and stirred for 2 days. The solid was collected by filtration and washed with cold ethanol to afford the title compound (5.69 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). at room temperature stirred for an additional 3 h The reaction mixture was concentrated in vacuo stirred for 2 days The solid was collected by filtration washed with cold ethanol

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

Procedure: (S)-Epichlorohydrin (48.0 mL, 0.612 mol) was added to a stirred solution of piperazine sulfonamide (87.3 g, 0.532 mol) in ethanol (1.33 L) at room temperature. The reaction mixture was stirred for 18 h and the white solid precipitate which formed was collected by filtration and washed with ethanol to afford the title intermediate (107.76 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). the white solid precipitate which formed was collected by filtration washed with ethanol

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

Procedure: (R)-Epichlorohydrin (3.10 mL, 39.5 mmol) was added to a stirred solution of piperazine sulfonamide. TFA (10.0 g, 35.9 mmol) and diisopropylethylamine (6.26 mL, 35.9 mmol) in ethanol (150 mL) at room temperature. The reaction mixture was stirred for 18 h and a further amount of (R)-epichlorohydrin was added (0.28 mL, 3.6 mmol) and stirred for an additional 3 h. The reaction mixture was concentrated in vacuo and the white solid was suspended in ethanol (150 mL) and stirred for 2 days. The solid was collected by filtration and washed with cold ethanol to afford the title compound (5.69 g) as a white solid which was used without further purification. (m/z): [M+H]+ calcd for C8H17ClN2O3S, 257.07; found 257.2. 1H NMR (DMSO-d6): δ (ppm) 2.37 (dd, 1H), 2.45 (dd, 1H), 2.50-2.58 (m, 4H), 2.86 (s, 3H), 3.09 (m, 4H), 3.55 (dd, 1H), 3.65 (dd, 1H), 3.84 (m, 1H), 5.09 (d, 1H). at room temperature stirred for an additional 3 h The reaction mixture was concentrated in vacuo stirred for 2 days The solid was collected by filtration washed with cold ethanol