N-[(2-chlorophenyl)methyl]hydroxylamine

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:

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: A stirred solution of 10.0 grams (0.063 mole) of N-(2-chlorophenyl)methylhydroxylamine (Example 1, Step A-2) and 12.9 grams (0.19 mole) of imidazole in 50 ml of dry dimethylformamide was cooled in an ice-water bath. To this stirred solution was added dropwise during a 20 minute period 10.6 grams (0.07 mole) of tert-butyldimethylsilyl chloride in 25 ml of dry dimethylformamide. During the addition the reaction mixture temperature was maintained at 5°. Upon completion of addition the reaction mixture was allowed to warm to ambient temperature at which it was stirred for 18 hours. Most of the dimethylformamide was removed from the reaction mixture under water aspirator pressure. The residue was taken up in 300 ml of methylene chloride and washed with three 100-ml portions of water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give on cooling a semi-solid residue. A sample of the semi-solid was slurried with hexane and the insolubles collected by filtration. The filtrate was concentrated to give an oil residue. The above procedure was repeated on the remainder of the semi-solid using 75 ml of hexane. The hexane filtrate was concentrated under reduced pressure to give an oil residue. The oil was distilled under reduced pressure to give 10.2 grams of [(2-chlorophenyl)methyl]-[dimethyl(1,1-dimethylethyl)silyloxy]amine; bp 88°-89°/0.7 Pa. During the addition the reaction mixture temperature was maintained at 5° Upon completion of addition the reaction mixture Most of the dimethylformamide was removed from the reaction mixture under water aspirator pressure washed with three 100-ml portions of water The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to give on cooling a semi-solid residue the insolubles collected by filtration The filtrate was concentrated to give an oil residue The hexane filtrate was concentrated under reduced pressure to give an oil residue The oil was distilled under reduced pressure

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

Procedure: To a stirred solution of 3.0 grams (0.025 mole) of 3-hydroxy-2,2-dimethylpropionic acid (Example 12, Step A) and 3.9 grams (0.025 mole) of N-(2-chlorophenyl)methyl hydroxylamine (Example 1, Step A-2) in 65 ml of ethanol was added dropwise a solution of 5.2 grams (0.025 mole) of dicyclohexylcarbodiimide in 25 ml of chloroform. Upon completion of addition the reaction mixture was stirred at ambient temperature for 60 hours. The reaction mixture was concentrated under reduced pressure to give a residual solid. The solid was recrystallized from ethanol, then from ethanol-water to give a solid; mp 229°-230°. The filtrates from the recrystallizations were combined and concentrated under high vacuum to give a residual oil. The residual oil was subjected to column chromatography. Elution was accomplished using 4:1--cyclohexane:ethyl acetate. The appropriate fraction was concentrated under reduced pressure to give a solid. The solid was recrystallized from ethyl acetatehexane to give 0.51 gram of N-[(2-chlorophenyl)methyl]-N,3-dihydroxy-2,2-dimethylpropanamide; mp 130°-132°. The solid was recrystallized a second time from ethyl acetate-cyclohexane to raise the mp to 131°-132°. Upon completion of addition the reaction mixture The reaction mixture was concentrated under reduced pressure to give a residual solid The solid was recrystallized from ethanol from ethanol-water to give a solid The filtrates from the recrystallizations concentrated under high vacuum to give a residual oil Elution The appropriate fraction was concentrated under reduced pressure to give a solid The solid was recrystallized from ethyl acetatehexane

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

Procedure: This compound was prepared in the manner of Example 1, Step C, using 6.0 grams (0.05 mole) of trimethylacetyl chloride, 9.5 grams (0.06 mole) of N-(2-chlorophenylmethyl)hydroxylamine (prepared in Example I, Step A), and 14.2 grams (0.18 mole) of pyridine in 60 ml of methylene chloride. The crude product was recrystallized from hexane to give 3.5 grams of N-(2-chlorophenyl)methyl-N-hydroxy-2,2-dimethylpropanamide; mp 100°-102°. This compound was prepared in the manner of Example 1, Step C The crude product was recrystallized from hexane

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

Procedure: Under an argon atmosphere a stirred solution of 10.2 grams (0.065 mole) of N-(2-chlorophenylmethyl)hydroxylamine and 6.1 grams (0.077 mole) of pyridine in 80 ml of methylene chloride was cooled to -10°. A solution of 10.0 grams (0.065 mole) of 3-chloro-2,2-dimethylpropionyl chloride in 20 ml of methylene chloride was added dropwise to the hydroxylamine solution during a 20 minute period. Upon completion of addition the reaction mixture was allowed to warm to ambient temperature where it was stirred for 16 hours. The reaction mixture was diluted with 100 ml of methylene chloride and washed with 100 ml of water, 100 ml of aqueous 10% hydrochloric acid, and finally 100 ml of water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give a residual oil. The oil was taken up in 25 ml of hexane and cooled in an icewater bath. The resultant solid precipitate was collected by filtration and recrystallized from hexaneethyl acetate to give 3.7 grams of 3-chloro-N-(2-chlorophenyl)methyl-N-hydroxy-2,2-dimethylpropanamide; mp 108°-110°. Upon completion of addition the reaction mixture washed with 100 ml of water, 100 ml of aqueous 10% hydrochloric acid, and finally 100 ml of water The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to give a residual oil cooled in an icewater bath The resultant solid precipitate was collected by filtration recrystallized from hexaneethyl acetate