2-methylpropyl carbamate

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

Procedure: To a stirred, biphasic mixture of 4-(3,6-dihydro-2H-thiopyran-4-yl)-3,5-difluorobenzenamine (Step 4, 3.90 g, 17.2 mmol) in THF/water (2:1, 103 mL) is added sodium bicarbonate (2.88 g, 34.3 mmol) followed by isobutyl carbamate (2.45 mL, 18.9 mmol) dropwise. The reaction mixture is stirred at ambient temperature for 7 h and is then concentrated under reduced pressure, diluted with EtOAc (100 mL) and H2O (50 mL), and the layers are separated. The organic phase is washed with H2O (25 mL) and saline (25 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge, eluting with 5-10% EtOAc/Hexanes, affords the title compound, mp 136-137° C.; MS (ESI−) for C16H19F2NO2S m/z 326 (M−H)−. is then concentrated under reduced pressure diluted with EtOAc (100 mL) and H2O (50 mL) the layers are separated The organic phase is washed with H2O (25 mL) and saline (25 mL) dried over anhydrous magnesium sulfate concentrated under reduced pressure Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge eluting with 5-10% EtOAc/Hexanes

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

Procedure: To a stirred, biphasic mixture of 4-(3,6-dihydro-2H-thiopyran-4-yl)-3,5-difluorobenzenamine (Step 4, 3.90 g, 17.2 mmol) in THF/water (2:1, 103 mL) is added sodium bicarbonate (2.88 g, 34.3 mmol) followed by isobutyl carbamate (2.45 mL, 18.9 mmol) dropwise. The reaction mixture is stirred at ambient temperature for 7 h and is then concentrated under reduced pressure, diluted with EtOAc (100 mL) and H2O (50 mL), and the layers are separated. The organic phase is washed with H2O (25 mL) and saline (25 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge, eluting with 5–10% EtOAc/Hexanes, affords the title compound, mp 136–137° C.; MS (ESI−) for C16H19F2NO2S m/z 326 (M−H)−. is then concentrated under reduced pressure diluted with EtOAc (100 mL) and H2O (50 mL) the layers are separated The organic phase is washed with H2O (25 mL) and saline (25 mL) dried over anhydrous magnesium sulfate concentrated under reduced pressure Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge eluting with 5–10% EtOAc/Hexanes

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

Procedure: To a stirred, biphasic mixture of 4-(3,6-dihydro-2H-thiopyran-4-yl)-3,5-difluorobenzenamine (Step 4, 3.90 g, 17.2 mmol) in THF/water (2:1, 103 mL) is added sodium bicarbonate (2.88 g, 34.3 mmol) followed by isobutyl carbamate (2.45 mL, 18.9 mmol) dropwise. The reaction mixture is stirred at ambient temperature for 7 h and is then concentrated under reduced pressure, diluted with EtOAc (100 mL) and H2O (50 mL), and the layers are separated. The organic phase is washed with H2O (25 mL) and saline (25 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge, eluting with 5–10% EtOAc/Hexanes, affords the title compound, mp 136–137° C.; MS (ESI−) for C16H19F2NO2S m/z 326 (M−H)−. is then concentrated under reduced pressure diluted with EtOAc (100 mL) and H2O (50 mL) the layers are separated The organic phase is washed with H2O (25 mL) and saline (25 mL) dried over anhydrous magnesium sulfate concentrated under reduced pressure Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge eluting with 5–10% EtOAc/Hexanes

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

Procedure: To a stirred, biphasic mixture of 4-(3,6-dihydro-2H-thiopyran-4-yl)-3,5-difluorobenzenamine (Step 4, 3.90 g, 17.2 mmol) in THF/water (2:1, 103 mL) is added sodium bicarbonate (2.88 g, 34.3 mmol) followed by isobutyl carbamate (2.45 mL, 18.9 mmol) dropwise. The reaction mixture is stirred at ambient temperature for 7 h and is then concentrated under reduced pressure, diluted with EtOAc (100 mL) and H2O (50 mL), and the layers are separated. The organic phase is washed with H2O (25 mL) and saline (25 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge, eluting with 5-10% EtOAc/Hexanes, affords the title compound, mp 136-137° C.; MS (ESI−) for C16H19F2NO2S m/z 326 (M−H)−. is then concentrated under reduced pressure diluted with EtOAc (100 mL) and H2O (50 mL) the layers are separated The organic phase is washed with H2O (25 mL) and saline (25 mL) dried over anhydrous magnesium sulfate concentrated under reduced pressure Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge eluting with 5-10% EtOAc/Hexanes

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

Procedure: To a stirred, biphasic mixture of 4-(3,6-dihydro-2H-thiopyran-4-yl)-3,5-difluorobenzenamine (Step 4, 3.90 g, 17.2 mmol) in THF/water (2:1, 103 mL) is added sodium bicarbonate (2.88 g, 34.3 mmol) followed by isobutyl carbamate (2.45 mL, 18.9 mmol) dropwise. The reaction mixture is stirred at ambient temperature for 7 h and is then concentrated under reduced pressure, diluted with EtOAc (100 mL) and H2O (50 mL), and the layers are separated. The organic phase is washed with H2O (25 mL) and saline (25 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge, eluting with 5-10% EtOAc/Hexanes, affords the title compound, mp 136-137° C.; MS (ESI−) for C16H19F2NO2S m/z 326 (M−H)−. is then concentrated under reduced pressure diluted with EtOAc (100 mL) and H2O (50 mL) the layers are separated The organic phase is washed with H2O (25 mL) and saline (25 mL) dried over anhydrous magnesium sulfate concentrated under reduced pressure Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge eluting with 5-10% EtOAc/Hexanes

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

Procedure: To a stirred, biphasic mixture of 4-(3,6-dihydro-2H-thiopyran-4-yl)-3,5-difluorobenzenamine (Step 4, 3.90 g, 17.2 mmol) in THF/water (2:1, 103 mL) is added sodium bicarbonate (2.88 g, 34.3 mmol) followed by isobutyl carbamate (2.45 mL, 18.9 mmol) dropwise. The reaction mixture is stirred at ambient temperature for 7 h and is then concentrated under reduced pressure, diluted with EtOAc (100 mL) and H2O (50 mL), and the layers are separated. The organic phase is washed with H2O (25 mL) and saline (25 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge, eluting with 5–10% EtOAc/Hexanes, affords the title compound, mp 136–137° C.; MS (ESI−) for C16H19F2NO2S m/z 326 (M−H)−. is then concentrated under reduced pressure diluted with EtOAc (100 mL) and H2O (50 mL) the layers are separated The organic phase is washed with H2O (25 mL) and saline (25 mL) dried over anhydrous magnesium sulfate concentrated under reduced pressure Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge eluting with 5–10% EtOAc/Hexanes