3,4-dihydro-1H-2lambda6,1-benzothiazine 2,2-dioxide

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

Procedure: NBS (1.5 g, 8.2 mmol) was added to a solution of 3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (1.5 g, 8.2 mmol) in DMF (15 mL). The reaction mixture was stirred overnight at ambient temperature followed by addition of water (200 mL) and EtOAc (100 mL). The two layers were separated and the aqueous phase was extracted with EtOAc (100 mL×3). The combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:3) to afford 6-bromo-3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (1.7 g, 79% yield). The two layers were separated the aqueous phase was extracted with EtOAc (100 mL×3) The combined organic phases were washed with brine (200 mL×3) dried over anhydrous sodium sulfate concentrated The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:3)

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

Procedure: Freshly polished lithium flakes (2.0 g, 0.28 mol) were added to a solution of 1-benzyl-1H-benzo[c][1,2]thiazine 2,2-dioxide (6.5 g, 24 mmol) in THF (120 mL)/EtOH (12 mL) and liquid NH3 (150 mL) at −40° C. with stirring over 0.5 h. The reaction was quenched with NH4Cl powder (10 g). Water (200 mL) and EtOAc (200 mL) were added. The two layers were separated and the aqueous phase was extracted with EtOAc (100 mL×3). The combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:4) to afford 3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (1.5 g, 34% yield). The reaction was quenched with NH4Cl powder (10 g) Water (200 mL) and EtOAc (200 mL) were added The two layers were separated the aqueous phase was extracted with EtOAc (100 mL×3) The combined organic phases were washed with brine (200 mL×3) dried over anhydrous sodium sulfate concentrated The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:4)

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

Procedure: NBS (1.5 g, 8.2 mmol) was added to a solution of 3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (1.5 g, 8.2 mmol) in DMF (15 mL). The reaction mixture was stirred overnight at ambient temperature followed by addition of water (200 mL) and EtOAc (100 mL). The two layers were separated and the aqueous phase was extracted with EtOAc (100 mL×3). The combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:3) to afford 6-bromo-3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (1.7 g, 79% yield). The two layers were separated the aqueous phase was extracted with EtOAc (100 mL×3) The combined organic phases were washed with brine (200 mL×3) dried over anhydrous sodium sulfate concentrated The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:3)

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

Procedure: Freshly polished lithium flakes (2.0 g, 0.28 mol) were added to a solution of 1-benzyl-1H-benzo[c][1,2]thiazine 2,2-dioxide (6.5 g, 24 mmol) in THF (120 mL)/EtOH (12 mL) and liquid NH3 (150 mL) at −40° C. with stirring over 0.5 h. The reaction was quenched with NH4Cl powder (10 g). Water (200 mL) and EtOAc (200 mL) were added. The two layers were separated and the aqueous phase was extracted with EtOAc (100 mL×3). The combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:4) to afford 3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (1.5 g, 34% yield). The reaction was quenched with NH4Cl powder (10 g) Water (200 mL) and EtOAc (200 mL) were added The two layers were separated the aqueous phase was extracted with EtOAc (100 mL×3) The combined organic phases were washed with brine (200 mL×3) dried over anhydrous sodium sulfate concentrated The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:4)

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

Procedure: A solution of 1H-benzo[c][1,2]thiazine 2,2-dioxide (0.381 g, 2.1 mmol) and 10% palladium on carbon (0.05 g) in anhydrous methanol (6 mL) was placed under a hydrogen filled balloon and stirred at room temperature for 17 hours. The mixture was filtered through Celite and concentrated to give a white solid (0.366 g, 95%). 1H NMR (CDCl3, 300 MHz) δ 7.25-7.16 (m, 2H), 7.07-7.01 (m, 1H), 6.76-6.73 (d, 1H, J=8.4 Hz), 3.51-3.46 (t, 2H, J=6.8 Hz), 3.34-3.29 (br t, 1H, J=6.9 Hz). The mixture was filtered through Celite concentrated

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

Procedure: NBS (1.5 g, 8.2 mmol) was added to a solution of 3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (1.5 g, 8.2 mmol) in DMF (15 mL). The reaction mixture was stirred overnight at ambient temperature followed by addition of water (200 mL) and EtOAc (100 mL). The two layers were separated and the aqueous phase was extracted with EtOAc (100 mL×3). The combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:3) to afford 6-bromo-3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (1.7 g, 79% yield). The two layers were separated the aqueous phase was extracted with EtOAc (100 mL×3) The combined organic phases were washed with brine (200 mL×3) dried over anhydrous sodium sulfate concentrated The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:3)

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

Procedure: Freshly polished lithium flakes (2.0 g, 0.28 mol) were added to a solution of 1-benzyl-1H-benzo[c][1,2]thiazine 2,2-dioxide (6.5 g, 24 mmol) in THF (120 mL)/EtOH (12 mL) and liquid NH3 (150 mL) at −40° C. with stirring over 0.5 h. The reaction was quenched with NH4Cl powder (10 g). Water (200 mL) and EtOAc (200 mL) were added. The two layers were separated and the aqueous phase was extracted with EtOAc (100 mL×3). The combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:4) to afford 3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (1.5 g, 34% yield). The reaction was quenched with NH4Cl powder (10 g) Water (200 mL) and EtOAc (200 mL) were added The two layers were separated the aqueous phase was extracted with EtOAc (100 mL×3) The combined organic phases were washed with brine (200 mL×3) dried over anhydrous sodium sulfate concentrated The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:4)