N-(2-tert-butylphenyl)acetamide

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(2-tert-butylphenyl)acetamide (Reference Example 17, 5.93 g, 31.0 mmol) and sulfuryl chloride (10.5 g, 77.5 mmol) in acetic acid (190 mL) was stirred at 50° C. for 16 h. The reaction mixture was partitioned between ethyl acetate and water, and the organic layer was washed with 10% aqueous NaHCO3, and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting solid was recrystallized from toluene/diethyl ether to give the title compound (3.73 g) as a white solid. The mother liquid was concentrated under reduced pressure and the residue was purified by flash column chromatography (silica gel, 4:1-1:4 hexane/ethyl acetate) to provide the title compound (1.05 g) as a white solid. The reaction mixture was partitioned between ethyl acetate and water the organic layer was washed with 10% aqueous NaHCO3, and saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting solid was recrystallized from toluene/diethyl ether

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(2-tert-butylphenyl)acetamide (Reference Example 17, 5.93 g, 31.0 mmol) and sulfuryl chloride (10.5 g, 77.5 mmol) in acetic acid (190 mL) was stirred at 50° C. for 16 h. The reaction mixture was partitioned between ethyl acetate and water, and the organic layer was washed with 10% aqueous NaHCO3, and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting solid was recrystallized from toluene/diethyl ether to give the title compound (3.73 g) as a white solid. The mother liquid was concentrated under reduced pressure and the residue was purified by flash column chromatography (silica gel, 4:1-1:4 hexane/ethyl acetate) to provide the title compound (1.05 g) as a white solid. The reaction mixture was partitioned between ethyl acetate and water the organic layer was washed with 10% aqueous NaHCO3, and saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting solid was recrystallized from toluene/diethyl ether

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

Procedure: To a solution of 2-tert-butylaniline (5.0 g, 33.5 mmol) and triethylamine (11.2 g, 110.6 mmol) in THF (350 mL) was added acetyl chloride (2.89 g, 36.9 mmol). After being stirred at room temperature for 3 h, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting white solid was triturated with hexane/ethyl acetate to give the title compound (6.13 g) as a white crystalline powder. the reaction mixture was partitioned between ethyl acetate and water The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting white solid was triturated with hexane/ethyl acetate

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

Procedure: Concentrated sulfuric acid (30 mL) was cooled to 0° C. and solid N-(2-tert-butylphenyl)acetamide (1.0 g, 5.2 mmol) was added in several portions. To the resulting solution was added KNO3 (578 mg, 5.7 mmol). The reaction mixture was allowed to warm to rt over 2 h and then stirred at rt overnight. The reaction mixture was poured over ice and a white precipitate formed. The precipitate was isolated by filtration (1.04 g, 84%). LCMS: (FA) ES+ 237.2 (M+1), ES− 235.1 (M−1). The reaction mixture was poured over ice a white precipitate formed The precipitate was isolated by filtration (1.04 g, 84%)

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

Procedure: A solution of 2-tert-butylaniline (2.0 g, 2.1 mL, 13.4 mmol) and TEA (2.8 mL, 20.1 mmol) in DCM (100 mL) was cooled to 0° C. Acetyl chloride (1.0 mL, 14.7 mmol) was added dropwise. The resulting solution was allowed to stir and warm to rt over 2 h. The reaction mixture was diluted with water and DCM. The organic phase was washed with 1N HCl and brine, dried over Na2SO4, filtered and concentrated to give the title compound as a white solid (2.73 g, >100%). 1H NMR (400 MHz, CDCl3) δ: 7.51-7.53 (m, 1H), 7.39-7.41 (m, 1H), 7.14-7.24 (m, 2H), 2.21 (s, 2.2H), 1.92 (s, 0.9H), and 1.41 (s, 9H). The organic phase was washed with 1N HCl and brine dried over Na2SO4 filtered concentrated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(2-tert-butylphenyl)acetamide (Reference Example 17, 5.93 g, 31.0 mmol) and sulfuryl chloride (10.5 g, 77.5 mmol) in acetic acid (190 mL) was stirred at 50° C. for 16 h. The reaction mixture was partitioned between ethyl acetate and water, and the organic layer was washed with 10% aqueous NaHCO3, and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting solid was recrystallized from toluene/diethyl ether to give the title compound (3.73 g) as a white solid. The mother liquid was concentrated under reduced pressure and the residue was purified by flash column chromatography (silica gel, 4:1-1:4 hexane/ethyl acetate) to provide the title compound (1.05 g) as a white solid. The reaction mixture was partitioned between ethyl acetate and water the organic layer was washed with 10% aqueous NaHCO3, and saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting solid was recrystallized from toluene/diethyl ether

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

Procedure: To a solution of 2-tert-butylaniline (5.0 g, 33.5 mmol) and triethylamine (11.2 g, 110.6 mmol) in THF (350 mL) was added acetyl chloride (2.89 g, 36.9 mmol). After being stirred at room temperature for 3 h, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting white solid was triturated with hexane/ethyl acetate to give the title compound (6.13 g) as a white crystalline powder. the reaction mixture was partitioned between ethyl acetate and water The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting white solid was triturated with hexane/ethyl acetate