3-hydroxy-N-methylbenzenesulfonamide

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

Procedure: N-Methyl-3-hydroxybenzene sulfonamide (175 mg, 0.94 mmole) in 15 mL of DMF was treated with Cs2CO3 (305 mg, 0.94 mmole), and stirred for 45 minutes. A solution of 3-Chloro-1-propanol tosylate (223 mg, 0.90 mmole) in 3 mL of DMF was added. The reaction was heated at 55° for 3 hours, and stirred at 23° for 16 hours. The reaction was diluted with H2O and extracted with Et2O. The extracts were washed with H2O, dried and the solvent removed. The residue was chromatographed on a silica gel column, and elution with 30% EtOAc in hexane gave the titled product, 75 mg (30%). MS (ESI) 264 (MH+). The reaction was heated at 55° for 3 hours stirred at 23° for 16 hours extracted with Et2O The extracts were washed with H2O dried the solvent removed The residue was chromatographed on a silica gel column, and elution with 30% EtOAc in hexane

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

Procedure: N-Methyl-3-aminobenzene sulfonamide (488 mg, 2.62 mmole) was dissolved in a mixture of 10 mL of H2O and 2 mL of conc. H2SO4, and was cooled to −5°. A solution of NaNO2 (207 mg, 3 mmole) in 2 mL of H2O was added dropwise at such a rate that the temperature doesn't exceed 0°. The reaction was stirred for 10 minutes, urea (100 mg) was added, and the reaction was stirred an additional 10 minutes. The cold solution of diazo compound was slowly added with stirring to a 0° solution of Cu(NO3)2 dihydrate (10.3 g, 43 mmole) and Cu2O (363 mg) in 100 mL of H2O. Stirring was continued for 30 minutes as the temperature was allowed to warm to 23°. The heterogeneous reaction was extracted with Et2O, and the extracts were extracted with 0.2N NaOH. The basic extracts were washed with Et2O, acidified, and extracted with CH2Cl2. The extracts were dried, and the solvent removed. The residue was chromatographed on a silica gel column, and elution with 50% EtOAc in hexane gave the titled product, 175 mg (36%). MS (ESI) 188 (MH+). was cooled to −5° the reaction was stirred an additional 10 minutes Stirring was continued for 30 minutes as the temperature to warm to 23° The heterogeneous reaction was extracted with Et2O the extracts were extracted with 0.2N NaOH The basic extracts were washed with Et2O extracted with CH2Cl2 The extracts were dried the solvent removed The residue was chromatographed on a silica gel column, and elution with 50% EtOAc in hexane

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

Procedure: N-Methyl-3-aminobenzene sulfonamide (488 mg, 2.62 mmole) was dissolved in a mixture of 10 mL of H2O and 2 mL of conc. H2SO4, and was cooled to −5°. A solution of NaNO2 (207 mg, 3 mmole) in 2 mL of H2O was added dropwise at such a rate that the temperature doesn't exceed 0°. The reaction was stirred for 10 minutes, urea (100 mg) was added, and the reaction was stirred an additional 10 minutes. The cold solution of diazo compound was slowly added with stirring to a 0° solution of Cu(NO3)2 dihydrate (10.3 g, 43 mmole) and Cu2O (363 mg) in 100 mL of H2O. Stirring was continued for 30 minutes as the temperature was allowed to warm to 23°. The heterogeneous reaction was extracted with Et2O, and the extracts were extracted with 0.2N NaOH. The basic extracts were washed with Et2O, acidified, and extracted with CH2Cl2. The extracts were dried, and the solvent removed. The residue was chromatographed on a silica gel column, and elution with 50% EtOAc in hexane gave the titled product, 175 mg (36%). MS (ESI) 188 (MH+). was cooled to −5° the reaction was stirred an additional 10 minutes Stirring was continued for 30 minutes as the temperature to warm to 23° The heterogeneous reaction was extracted with Et2O the extracts were extracted with 0.2N NaOH The basic extracts were washed with Et2O extracted with CH2Cl2 The extracts were dried the solvent removed The residue was chromatographed on a silica gel column, and elution with 50% EtOAc in hexane

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

Procedure: N-Methyl-3-hydroxybenzene sulfonamide (175 mg, 0.94 mmole) in 15 mL of DMF was treated with Cs2CO3 (305 mg, 0.94 mmole), and stirred for 45 minutes. A solution of 3-Chloro-1-propanol tosylate (223 mg, 0.90 mmole) in 3 mL of DMF was added. The reaction was heated at 55° for 3 hours, and stirred at 23° for 16 hours. The reaction was diluted with H2O and extracted with Et2O. The extracts were washed with H2O, dried and the solvent removed. The residue was chromatographed on a silica gel column, and elution with 30% EtOAc in hexane gave the titled product, 75 mg (30%). MS (ESI) 264 (MH+). The reaction was heated at 55° for 3 hours stirred at 23° for 16 hours extracted with Et2O The extracts were washed with H2O dried the solvent removed The residue was chromatographed on a silica gel column, and elution with 30% EtOAc in hexane

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

Procedure: N-Methyl-3-aminobenzene sulfonamide (488 mg, 2.62 mmole) was dissolved in a mixture of 10 mL of H2O and 2 mL of conc. H2SO4, and was cooled to −5°. A solution of NaNO2 (207 mg, 3 mmole) in 2 mL of H2O was added dropwise at such a rate that the temperature doesn't exceed 0°. The reaction was stirred for 10 minutes, urea (100 mg) was added, and the reaction was stirred an additional 10 minutes. The cold solution of diazo compound was slowly added with stirring to a 0° solution of Cu(NO3)2 dihydrate (10.3 g, 43 mmole) and Cu2O (363 mg) in 100 mL of H2O. Stirring was continued for 30 minutes as the temperature was allowed to warm to 23°. The heterogeneous reaction was extracted with Et2O, and the extracts were extracted with 0.2N NaOH. The basic extracts were washed with Et2O, acidified, and extracted with CH2Cl2. The extracts were dried, and the solvent removed. The residue was chromatographed on a silica gel column, and elution with 50% EtOAc in hexane gave the titled product, 175 mg (36%). MS (ESI) 188 (MH+). was cooled to −5° the reaction was stirred an additional 10 minutes Stirring was continued for 30 minutes as the temperature to warm to 23° The heterogeneous reaction was extracted with Et2O the extracts were extracted with 0.2N NaOH The basic extracts were washed with Et2O extracted with CH2Cl2 The extracts were dried the solvent removed The residue was chromatographed on a silica gel column, and elution with 50% EtOAc in hexane