2-chloro-N-(2,4-dichlorophenyl)-4,4-dimethyl-3-oxopentanamide

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

Procedure: Triethylamine (57.35 g, 566 mmol) was added to a stirred solution of N-[2-chloro-4,4,-dimethyl-3-oxopentanoyl]-2,4-dichloroaniline prepared as above (155.9 g, 483 mmol) and phenol (49.9 g, 530 mmol) in dry acetonitrile (1.3 L) under argon. After the addition had been completed, the mixture was heated at reflux for 7 hours. The reaction mixture was then cooled and the solvent was removed under reduced pressure. The residue was dissolved in methanol (300 mL) and allowed to stir at room temperature until crystallization began. After 2 hours, the mixture was cooled in an ice bath for a further 1 hour. The product was removed by filtration, washed with cold methanol, and dried to afford N-[4,4-dimethyl-3-oxo-2-phenoxypentanoyl]-2,4-dichloroaniline (99 g, 54% yield) as a white crystalline solid which melted at 112°-113.5° C. The structure of this compound was confirmed by mass spectroscopy and by 1H and 13C NMR spectroscopy. After the addition the mixture was heated at reflux for 7 hours The reaction mixture was then cooled the solvent was removed under reduced pressure The residue was dissolved in methanol (300 mL) the mixture was cooled in an ice bath for a further 1 hour The product was removed by filtration washed with cold methanol dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sulfuryl chloride (54.1 g, 0.4 mol) was added dropwise with vigorous stirring over a 60 minute period to a solution of N-[4,4-dimethyl-3-oxopentanoyl]-2,4-dichloroaniline, prepared as above (109 g, 0.378 mol) in dichloromethane (600 mL) at -10° C. The reaction mixture was maintained at this temperature for 3 hours after the addition had been completed. After this time, the mixture was allowed to warm to 0° C. and ice (approximately 50 mL) was added, with stirring. The organic layer was separated and washed with 50% saturated aqueous sodium chloride solution (2×500 mL), then dried over magnesium sulfate. Evaporation of the solvent afforded a brown oil which was stirred with ethanol (150 mL) to induce crystallization of the product. The resultant mixture was stored at 0° C. overnight. The solid product was removed by filtration, washed with cold ethanol and dried to afford N-[2-chloro-4,4,-dimethyl-3-oxopentanoyl]-2,4-dichloroaniline (104.2 g, 85.4% yield) as a white crystalline solid which melted at 64.5°-65.5° C. The structure of this compound was confirmed by mass spectroscopy and by 1H and 13C NMR spectroscopy. The reaction mixture was maintained at this temperature for 3 hours after the addition The organic layer was separated washed with 50% saturated aqueous sodium chloride solution (2×500 mL) dried over magnesium sulfate Evaporation of the solvent afforded a brown oil which crystallization of the product The solid product was removed by filtration washed with cold ethanol dried

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

Procedure: Triethylamine (57.35 g, 566 mmol) was added to a stirred solution of N-[2-chloro-4,4,-dimethyl-3-oxopentanoyl]-2,4-dichloroaniline prepared as above (155.9 g, 483 mmol) and phenol (49.9 g, 530 mmol) in dry acetonitrile (1.3 L) under argon. After the addition had been completed, the mixture was heated at reflux for 7 hours. The reaction mixture was then cooled and the solvent was removed under reduced pressure. The residue was dissolved in methanol (300 mL) and allowed to stir at room temperature until crystallization began. After 2 hours, the mixture was cooled in an ice bath for a further 1 hour. The product was removed by filtration, washed with cold methanol, and dried to afford N-[4,4-dimethyl-3-oxo-2-phenoxypentanoyl]-2,4-dichloroaniline (99 g, 54% yield) as a white crystalline solid which melted at 112°-113.5° C. The structure of this compound was confirmed by mass spectroscopy and by 1H and 13C NMR spectroscopy. After the addition the mixture was heated at reflux for 7 hours The reaction mixture was then cooled the solvent was removed under reduced pressure The residue was dissolved in methanol (300 mL) the mixture was cooled in an ice bath for a further 1 hour The product was removed by filtration washed with cold methanol dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sulfuryl chloride (54.1 g, 0.4 mol) was added dropwise with vigorous stirring over a 60 minute period to a solution of N-[4,4-dimethyl-3-oxopentanoyl]-2,4-dichloroaniline, prepared as above (109 g, 0.378 mol) in dichloromethane (600 mL) at -10° C. The reaction mixture was maintained at this temperature for 3 hours after the addition had been completed. After this time, the mixture was allowed to warm to 0° C. and ice (approximately 50 mL) was added, with stirring. The organic layer was separated and washed with 50% saturated aqueous sodium chloride solution (2×500 mL), then dried over magnesium sulfate. Evaporation of the solvent afforded a brown oil which was stirred with ethanol (150 mL) to induce crystallization of the product. The resultant mixture was stored at 0° C. overnight. The solid product was removed by filtration, washed with cold ethanol and dried to afford N-[2-chloro-4,4,-dimethyl-3-oxopentanoyl]-2,4-dichloroaniline (104.2 g, 85.4% yield) as a white crystalline solid which melted at 64.5°-65.5° C. The structure of this compound was confirmed by mass spectroscopy and by 1H and 13C NMR spectroscopy. The reaction mixture was maintained at this temperature for 3 hours after the addition The organic layer was separated washed with 50% saturated aqueous sodium chloride solution (2×500 mL) dried over magnesium sulfate Evaporation of the solvent afforded a brown oil which crystallization of the product The solid product was removed by filtration washed with cold ethanol dried

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

Procedure: Triethylamine (57.35 g, 566 mmol) was added to a stirred solution of N-[2-chloro-4,4,-dimethyl-3-oxopentanoyl]-2,4-dichloroaniline prepared as above (155.9 g, 483 mmol) and phenol (49.9 g, 530 mmol) in dry acetonitrile (1.3 L) under argon. After the addition had been completed, the mixture was heated at reflux for 7 hours. The reaction mixture was then cooled and the solvent was removed under reduced pressure. The residue was dissolved in methanol (300 mL) and allowed to stir at room temperature until crystallization began. After 2 hours, the mixture was cooled in an ice bath for a further 1 hour. The product was removed by filtration, washed with cold methanol, and dried to afford N-[4,4-dimethyl-3-oxo-2-phenoxypentanoyl]-2,4-dichloroaniline (99 g, 54% yield) as a white crystalline solid which melted at 112°-113.5° C. The structure of this compound was confirmed by mass spectroscopy and by 1H and 13C NMR spectroscopy. After the addition the mixture was heated at reflux for 7 hours The reaction mixture was then cooled the solvent was removed under reduced pressure The residue was dissolved in methanol (300 mL) the mixture was cooled in an ice bath for a further 1 hour The product was removed by filtration washed with cold methanol dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sulfuryl chloride (54.1 g, 0.4 mol) was added dropwise with vigorous stirring over a 60 minute period to a solution of N-[4,4-dimethyl-3-oxopentanoyl]-2,4-dichloroaniline, prepared as above (109 g, 0.378 mol) in dichloromethane (600 mL) at -10° C. The reaction mixture was maintained at this temperature for 3 hours after the addition had been completed. After this time, the mixture was allowed to warm to 0° C. and ice (approximately 50 mL) was added, with stirring. The organic layer was separated and washed with 50% saturated aqueous sodium chloride solution (2×500 mL), then dried over magnesium sulfate. Evaporation of the solvent afforded a brown oil which was stirred with ethanol (150 mL) to induce crystallization of the product. The resultant mixture was stored at 0° C. overnight. The solid product was removed by filtration, washed with cold ethanol and dried to afford N-[2-chloro-4,4,-dimethyl-3-oxopentanoyl]-2,4-dichloroaniline (104.2 g, 85.4% yield) as a white crystalline solid which melted at 64.5°-65.5° C. The structure of this compound was confirmed by mass spectroscopy and by 1H and 13C NMR spectroscopy. The reaction mixture was maintained at this temperature for 3 hours after the addition The organic layer was separated washed with 50% saturated aqueous sodium chloride solution (2×500 mL) dried over magnesium sulfate Evaporation of the solvent afforded a brown oil which crystallization of the product The solid product was removed by filtration washed with cold ethanol dried