3-CHLORO-N-HYDROXY-2,2-DIMETHYL-PROPANAMIDE

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of hydroxylamine hydrochloride (50.0 g, 0.7195 mol) in 150 mL of water, 50% aqueous sodium hydroxide solution is added dropwise until a pH of 7.0-7.2 is obtained. The solution is cooled to 20°-25° C. and 3-chloropivaloyl chloride (100.0 g, 0.6426 mol) is added dropwise maintaining a pH of 7.0-7.2 with 50% aqueous sodium hydroxide solution and a reaction pot temperature <30° C. The total addition time is 1 hour. This yellow slurry is stirred at room temperature overnight then diluted with water (200 mL). The hydroxamic acid is extracted with ethyl acetate (2×200 mL) and washed with water (200 mL). The organic layer is dried over magnesium sulfate and concentrated to 46.3 g of the title compound as a yellow solid and used without further purification. is obtained The solution is cooled to 20°-25° C. a reaction pot temperature <30° C The total addition time The hydroxamic acid is extracted with ethyl acetate (2×200 mL) washed with water (200 mL) The organic layer is dried over magnesium sulfate concentrated to 46.3 g of the title compound as a yellow solid used without further purification

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

Procedure: To a solution of hydroxylamine hydrochloride (50.0 g, 0.7195 mol) in 150 mL of water, 50% aqueous sodium hydroxide solution is added dropwise until a pH of 7.0-7.2 is obtained. The solution is cooled to 20°-25° C. and 3-chloropivaloyl chloride (100.0 g, 0.6426 mol) is added dropwise maintaining a pH of 7.0-7.2 with 50% aqueous sodium hydroxide solution and a reaction pot temperature <30° C. The total addition time is 1 hour. This yellow slurry is stirred at room temperature overnight then diluted with water (200 mL). The hydroxamic acid is extracted with ethyl acetate (2×200 mL) and washed with water (200 mL). The organic layer is dried over magnesium sulfate and concentrated to 46.3 g of the title compound as a yellow solid and used without further purification. is obtained The solution is cooled to 20°-25° C. a reaction pot temperature <30° C The total addition time The hydroxamic acid is extracted with ethyl acetate (2×200 mL) washed with water (200 mL) The organic layer is dried over magnesium sulfate concentrated to 46.3 g of the title compound as a yellow solid used without further purification

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A stirred solution of 28.0 grams (0.40 mole) of hydroxylamine hydrochloride in 60 ml of water was cooled to 0° and a solution of 16.0 grams (0.40 mole) of sodium hydroxide in 40 ml of water was added dropwise while maintaining the temperature of the reaction mixture at 0°-5°. Upon completion of addition 31.0 grams (0.20 mole) of 3-chloro-2,2-dimethylpropionyl chloride was added dropwise during a 45-minute period while maintaining the temperature of the reaction mixture at -3° to -5°. Upon completion of addition the reaction mixture was maintained at 5° for one hour, then was allowed to warm to ambient temperature where it was stirred for 16 hours. A white solid precipitate was collected by filtration and air-dried. The dried solid was recrystallized from ethanol-water to give 12.4 grams of 3-chloro-N-hydroxy-2,2-dimethylpropanamide; mp 148°-151°, decomposes. while maintaining the temperature of the reaction mixture at 0°-5° was added dropwise during a 45-minute period while maintaining the temperature of the reaction mixture at -3° to -5° Upon completion of addition the reaction mixture was maintained at 5° for one hour A white solid precipitate was collected by filtration air-dried The dried solid was recrystallized from ethanol-water

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

Procedure: A two liter resin kettle was equipped with two inlet tubes, a thermometer, stirring paddle, pH probes and a cooling jacket. A solution of hydroxylamine sulfate (264 g, 1.61 moles) and ethyl xanthic acid, potassium salt (0.5 g, 0.003 mole) in 700 ml of water was added to the kettle and the stirrer started. One of the inlet tubes was connected through a metering pump to a reservoir containing an aqueous 50% sodium hydroxide solution. The addition of base to the reaction mixture was regulated by an electronic pH meter/controller connected to the pump and pH probe and set for pH of 7.2. Aqueous base was delivered to the reactor until that pH was attained. The other inlet tube was connected through a metering pump to a reservoir containing 3-chloro-2,2-dimethylpropionyl chloride (286 g, 1.84 moles). The acid chloride was added to the reaction mixture during a period of 2.5 hours at a temperatue of 28° C., maintaining a pH of 7.2 by simultaneous addition of base. The reaction slurry was then vacuum filtered and the filter cake dried. The dried filter cake weighted 293 g. An aliquot of the filter cake was dissolved in a mixture of DMF and toluene. Analysis of the extract using GLPC indicated the yield of 3-chloro-N-hydroxy-2,2-dimethylpropanamide, based on the amount of 3-chloro-2,2-dimethylpropionyl chloride, was 85%. The addition of base to the reaction mixture maintaining a pH of 7.2 by simultaneous addition of base vacuum filtered the filter cake dried The dried filter cake An aliquot of the filter cake was dissolved in a mixture of DMF and toluene

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

Procedure: To a solution of hydroxylamine hydrochloride (50.0 g, 0.7195 mol) in 150 mL of water, 50% aqueous sodium hydroxide solution is added dropwise until a pH of 7.0-7.2 is obtained. The solution is cooled to 20°-25° C. and 3-chloropivaloyl chloride (100.0 g, 0.6426 mol) is added dropwise maintaining a pH of 7.0-7.2 with 50% aqueous sodium hydroxide solution and a reaction pot temperature <30° C. The total addition time is 1 hour. This yellow slurry is stirred at room temperature overnight then diluted with water (200 mL). The hydroxamic acid is extracted with ethyl acetate (2×200 mL) and washed with water (200 mL). The organic layer is dried over magnesium sulfate and concentrated to 46.3 g of the title compound as a yellow solid and used without further purification. is obtained The solution is cooled to 20°-25° C. a reaction pot temperature <30° C The total addition time The hydroxamic acid is extracted with ethyl acetate (2×200 mL) washed with water (200 mL) The organic layer is dried over magnesium sulfate concentrated to 46.3 g of the title compound as a yellow solid used without further purification