4-Acetamido-TEMPO

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

Procedure: 56.5 mg of (R)-3-((S)-2-(4,4-Dimethyl-3-(4-(3-phenylureido)-benzyl)-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetylamino)-3-methylpropanol were dissolved in a mixture of 3 ml of ethyl acetate, 1 ml of toluene and 1 ml of water with 10.8 mg of potassium bromide. After addition of a catalytic amount of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl (=4-acetamido-TEMPO), a mixture of 0.5 ml of sodium hypochlorite solution (13% strength), 0.5 ml of saturated sodium hydrogencarbonate solution and 1 ml of water was added dropwise at 0° C. The mixture was stirred at 0° C. for 25 minutes. After reaction was complete, the mixture was treated with ethyl acetate, and the organic phase was washed with sodium thiosulfate solution and dried over sodium sulfate. After filtration, the solvent was removed on a rotary evaporator and the residue was purified by reversed phase HPLC (water/acetonitrile). Yield: 15 mg. was added dropwise at 0° C After reaction the organic phase was washed with sodium thiosulfate solution dried over sodium sulfate After filtration the solvent was removed on a rotary evaporator the residue was purified by reversed phase HPLC (water/acetonitrile)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 10.0 g of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl, 16 ml of 70% aqueous tert-butylhydroperoxide and 0.67 g of molybdenum trioxide in 75 ml of cyclohexane is heated under reflux in a flask fitted with a Dean-Stark apparatus. After 6 ml of water is collected, the reaction mixture is transferred to a Fisher Porter apparatus and heated at 140° C. and 30 psi for 4 hours. The decolorized reaction mixture is filtered and the filtrate is washed with water, aqueous sodium sulfite, brine, dried (MgSO4) and concentrated to give 13.61 g of a white solid. Recrystallization from heptane affords 10.39 g of the title compound as a white crystalline solid, m.p. 140°-44° C. is heated under reflux in a flask fitted with a Dean-Stark apparatus After 6 ml of water is collected The decolorized reaction mixture is filtered the filtrate is washed with water, aqueous sodium sulfite, brine dried (MgSO4) concentrated

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 10.0 g of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl, 16 ml of 70% aqueous tert-butylhydroperoxide and 0.67 g of molybdenum trioxide in 75 ml of cyclohexane is heated under reflux in a flask fitted with a Dean-Stark apparatus. After 6 ml of water is collected, the reaction mixture is transferred to a Fisher Porter apparatus and heated at 140° C. and 30 psi for 4 hours. The decolorized reaction mixture is filtered and the filtrate is washed with water, aqueous sodium sulfite, brine, dried (MgSO4) and concentrated to give 13.61 g of a white solid. Recrystallization from heptane affords 10.39 g of the title compound as a white crystalline solid, m.p. 140°-44° C. is heated under reflux in a flask fitted with a Dean-Stark apparatus After 6 ml of water is collected The decolorized reaction mixture is filtered the filtrate is washed with water, aqueous sodium sulfite, brine dried (MgSO4) concentrated

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

Procedure: 56.5 mg of (R)-3-((S)-2-(4,4-Dimethyl-3-(4-(3-phenylureido)-benzyl)-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetylamino)-3-methylpropanol were dissolved in a mixture of 3 ml of ethyl acetate, 1 ml of toluene and 1 ml of water with 10.8 mg of potassium bromide. After addition of a catalytic amount of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl (=4-acetamido-TEMPO), a mixture of 0.5 ml of sodium hypochlorite solution (13% strength), 0.5 ml of saturated sodium hydrogencarbonate solution and 1 ml of water was added dropwise at 0° C. The mixture was stirred at 0° C. for 25 minutes. After reaction was complete, the mixture was treated with ethyl acetate, and the organic phase was washed with sodium thiosulfate solution and dried over sodium sulfate. After filtration, the solvent was removed on a rotary evaporator and the residue was purified by reversed phase HPLC (water/acetonitrile). Yield: 15 mg. was added dropwise at 0° C After reaction the organic phase was washed with sodium thiosulfate solution dried over sodium sulfate After filtration the solvent was removed on a rotary evaporator the residue was purified by reversed phase HPLC (water/acetonitrile)