N-[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]acetamide

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl)acetamide (3.36 g, 13.80 mmol) and concentrated hydrochloric acid (60 mL) was heated at 120° C. for 16.5 h. The mixture was cooled to rt and poured into ice water and the resulting mixture was adjusted to pH>12 with NaOH and extracted with EtOAc (80 mL×5). The combined organic phases were washed with brine (100 mL×2), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The residue was dissolved in concentrated hydrochloric acid (60 mL) and the mixture was stirred at 120° C. for 20 h. The reaction mixture was cooled to rt and 100 mL of water was added. The resulting mixture was washed with EtOAc (50 mL×3). The aqueous phase was adjusted to pH>11 with NaOH and extracted with EtOAc (50 mL×3). The combined organic phases were washed with brine (80 mL×2), dried over anhydrous Na2SO4 (20 g) and concentrated in vacuo to give the tile compound as a yellow solid (0.484 g, 17.4%). The compound was characterized by the following spectroscopic data: The mixture was cooled to rt extracted with EtOAc (80 mL×5) The combined organic phases were washed with brine (100 mL×2) dried over anhydrous Na2SO4 filtered The filtrate was concentrated in vacuo The residue was dissolved in concentrated hydrochloric acid (60 mL) The reaction mixture was cooled to rt 100 mL of water was added The resulting mixture was washed with EtOAc (50 mL×3) extracted with EtOAc (50 mL×3) The combined organic phases were washed with brine (80 mL×2) dried over anhydrous Na2SO4 (20 g) concentrated in vacuo

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-ol (8.61 g, 42.50 mmol), acetonitrile (13 mL, 255.0 mmol) and acetic acid (80 mL) was added sulfuric acid (13 mL) dropwise and the mixture was heated at 65° C. for 5 h. The mixture was cooled to rt and poured into ice water (400 mL) and the resulting mixture was adjusted to pH>11 with NaOH, and extracted with EtOAc (150 mL×3). The combined organic phases were washed with brine (150 mL×2), dried over anhydrous Na2SO4 (40 g) and filtered. The filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1) to give the title compound as a yellow solid (4.38 g, 42.1%). The compound was characterized by the following spectroscopic data: The mixture was cooled to rt extracted with EtOAc (150 mL×3) The combined organic phases were washed with brine (150 mL×2) dried over anhydrous Na2SO4 (40 g) filtered The filtrate was concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl)acetamide (3.36 g, 13.80 mmol) and concentrated hydrochloric acid (60 mL) was heated at 120° C. for 16.5 h. The mixture was cooled to rt and poured into ice water and the resulting mixture was adjusted to pH>12 with NaOH and extracted with EtOAc (80 mL×5). The combined organic phases were washed with brine (100 mL×2), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The residue was dissolved in concentrated hydrochloric acid (60 mL) and the mixture was stirred at 120° C. for 20 h. The reaction mixture was cooled to rt and 100 mL of water was added. The resulting mixture was washed with EtOAc (50 mL×3). The aqueous phase was adjusted to pH>11 with NaOH and extracted with EtOAc (50 mL×3). The combined organic phases were washed with brine (80 mL×2), dried over anhydrous Na2SO4 (20 g) and concentrated in vacuo to give the tile compound as a yellow solid (0.484 g, 17.4%). The compound was characterized by the following spectroscopic data: The mixture was cooled to rt extracted with EtOAc (80 mL×5) The combined organic phases were washed with brine (100 mL×2) dried over anhydrous Na2SO4 filtered The filtrate was concentrated in vacuo The residue was dissolved in concentrated hydrochloric acid (60 mL) The reaction mixture was cooled to rt 100 mL of water was added The resulting mixture was washed with EtOAc (50 mL×3) extracted with EtOAc (50 mL×3) The combined organic phases were washed with brine (80 mL×2) dried over anhydrous Na2SO4 (20 g) concentrated in vacuo

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-ol (8.61 g, 42.50 mmol), acetonitrile (13 mL, 255.0 mmol) and acetic acid (80 mL) was added sulfuric acid (13 mL) dropwise and the mixture was heated at 65° C. for 5 h. The mixture was cooled to rt and poured into ice water (400 mL) and the resulting mixture was adjusted to pH>11 with NaOH, and extracted with EtOAc (150 mL×3). The combined organic phases were washed with brine (150 mL×2), dried over anhydrous Na2SO4 (40 g) and filtered. The filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1) to give the title compound as a yellow solid (4.38 g, 42.1%). The compound was characterized by the following spectroscopic data: The mixture was cooled to rt extracted with EtOAc (150 mL×3) The combined organic phases were washed with brine (150 mL×2) dried over anhydrous Na2SO4 (40 g) filtered The filtrate was concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl)acetamide (3.36 g, 13.80 mmol) and concentrated hydrochloric acid (60 mL) was heated at 120° C. for 16.5 h. The mixture was cooled to rt and poured into ice water and the resulting mixture was adjusted to pH>12 with NaOH and extracted with EtOAc (80 mL×5). The combined organic phases were washed with brine (100 mL×2), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The residue was dissolved in concentrated hydrochloric acid (60 mL) and the mixture was stirred at 120° C. for 20 h. The reaction mixture was cooled to rt and 100 mL of water was added. The resulting mixture was washed with EtOAc (50 mL×3). The aqueous phase was adjusted to pH>11 with NaOH and extracted with EtOAc (50 mL×3). The combined organic phases were washed with brine (80 mL×2), dried over anhydrous Na2SO4 (20 g) and concentrated in vacuo to give the tile compound as a yellow solid (0.484 g, 17.4%). The compound was characterized by the following spectroscopic data: The mixture was cooled to rt extracted with EtOAc (80 mL×5) The combined organic phases were washed with brine (100 mL×2) dried over anhydrous Na2SO4 filtered The filtrate was concentrated in vacuo The residue was dissolved in concentrated hydrochloric acid (60 mL) The reaction mixture was cooled to rt 100 mL of water was added The resulting mixture was washed with EtOAc (50 mL×3) extracted with EtOAc (50 mL×3) The combined organic phases were washed with brine (80 mL×2) dried over anhydrous Na2SO4 (20 g) concentrated in vacuo

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-ol (8.61 g, 42.50 mmol), acetonitrile (13 mL, 255.0 mmol) and acetic acid (80 mL) was added sulfuric acid (13 mL) dropwise and the mixture was heated at 65° C. for 5 h. The mixture was cooled to rt and poured into ice water (400 mL) and the resulting mixture was adjusted to pH>11 with NaOH, and extracted with EtOAc (150 mL×3). The combined organic phases were washed with brine (150 mL×2), dried over anhydrous Na2SO4 (40 g) and filtered. The filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1) to give the title compound as a yellow solid (4.38 g, 42.1%). The compound was characterized by the following spectroscopic data: The mixture was cooled to rt extracted with EtOAc (150 mL×3) The combined organic phases were washed with brine (150 mL×2) dried over anhydrous Na2SO4 (40 g) filtered The filtrate was concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1)