N-(2-methylphenyl)hydroxylamine

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2.5 g (20 mmol) of N-(2-methylphenyl)-hydroxylamine (crude product, obtained according to Bamberger et al., Anm. Chem. 316 (1901), 278), 3.5 g (25 mmol) of K2CO3 and 3.5 g (22 mmol) of phenyl Chlorooformate in 20 ml of CH2Cl2 is stirred for 2 hours at room temperature. The reaction mixture is then extracted with water, dried over MgSO4 and evaporated down. The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate. There is obtained 2.0 g (8.2 mmol =42%) of the title compound as a colorless solid (mp=98° C.). The reaction mixture is then extracted with water dried over MgSO4 evaporated down The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 350 g (purity about 80%; 2.3 mol; prepared by a similar method to Bamberger et al., Ann. Chem. 316 (1901), 278) of N-(2-methylphenyl)hydroxylamine and 286.8 g (3.4 mol) of NaHCO3 in 700 ml of CH2Cl2 is treated with 447 g (2.85 mol) of phenyl chloroformate with vigorous stirring at about -10° C. The mixture is stirred for about 1 hour at -10° C. and 600 ml of water are then added dropwise, the temperature of the reaction mixture increasing to 5°-10° C. and a vigorous evolution of gas occurring. The aqueous phase is then separated off and extracted once more with CH2Cl2. The combined organic phases are extracted with water, dried over MgSO4 and concentrated. The residue crystallizes and is stirred with cyclohexane. 407 g (72%) of the title compound are obtained as a colorless solid. A mixture of 350 g (purity about 80% prepared by a similar method to Bamberger et al., Ann The mixture is stirred for about 1 hour at -10° C. the temperature of the reaction mixture increasing to 5°-10° C. The aqueous phase is then separated off extracted once more with CH2Cl2 The combined organic phases are extracted with water dried over MgSO4 concentrated The residue crystallizes is stirred with cyclohexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2.5 g (20 mmol) of N-(2-methylphenyl)-hydroxylamine (crude product, obtained according to Bamberger et al., Anm. Chem. 316 (1901), 278), 3.5 g (25 mmol) of K2CO3 and 3.5 g (22 mmol) of phenyl Chlorooformate in 20 ml of CH2Cl2 is stirred for 2 hours at room temperature. The reaction mixture is then extracted with water, dried over MgSO4 and evaporated down. The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate. There is obtained 2.0 g (8.2 mmol{circumflex over (=)}42%) of the title compound as a colorless solid (mp=98° C.). The reaction mixture is then extracted with water dried over MgSO4 evaporated down The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 350 g (purity about 80%; 2.3 mol; prepared by a similar method to Bamberger et al., Ann. Chem. 316 (1901), 278) of N-(2-methylphenyl)hydroxylamine and 286.8 g (3.4 mol) of NaHCO3 in 700 ml of CH2Cl2 is treated with 447 g (2.85 mol) of phenyl chloroformate with vigorous stirring at about -10° C. The mixture is stirred for about 1 hour at -10° C. and 600 ml of water are then added dropwise, the temperature of the reaction mixture increasing to 5-10° C. and a vigorous evolution of gas occurring. The aqueous phase is then separated off and extracted once more with CH2Cl2. The combined organic phases are extracted with water, dried over MgSO4 and concentrated. The residue crystallizes and is stirred with cyclohexane. 407 g (72%) of the title compound are obtained as a colorless solid. A mixture of 350 g (purity about 80% prepared by a similar method to Bamberger et al., Ann The mixture is stirred for about 1 hour at -10° C. the temperature of the reaction mixture increasing to 5-10° C. The aqueous phase is then separated off extracted once more with CH2Cl2 The combined organic phases are extracted with water dried over MgSO4 concentrated The residue crystallizes is stirred with cyclohexane

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 350 g (purity about 80%; 2.3 mol; prepared by a similar method to Bamberger et al., Ann. Chem. 316 (1901), 278) of N-(2-methylphenyl)hydroxylamine and 286.8 g (3.4 mol) of NaHCO3 in 700 ml of CH2Cl2 is treated with 447 g (2.85 mol) of phenyl chloroformate with vigorous stirring at about -10° C. The mixture is stirred for about 1 hour at -10° C. and 600 ml of water are then added dropwise, the temperature of the reaction mixture increasing to 5-10° C. and a vigorous evolution of gas occurring. The aqueous phase is then separated off and extracted once more with CH2Cl2. The combined organic phases are extracted with water, dried over MgSO4 and concentrated. The residue crystallizes and is stirred with cyclohexane. 407 g (72%) of the title compound are obtained as a colorless solid. A mixture of 350 g (purity about 80% prepared by a similar method to Bamberger et al., Ann The mixture is stirred for about 1 hour at -10° C. the temperature of the reaction mixture increasing to 5-10° C. The aqueous phase is then separated off extracted once more with CH2Cl2 The combined organic phases are extracted with water dried over MgSO4 concentrated The residue crystallizes is stirred with cyclohexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2.5 g (20 mmol) of N-(2-methylphenyl)-hydroxylamine (crude product, obtained according to Bamberger et al., Anm. Chem. 316 (1901), 278), 3.5 g (25 mmol) of K2CO3 and 3.5 g (22 mmol) of phenyl Chlorooformate in 20 ml of CH2Cl2 is stirred for 2 hours at room temperature. The reaction mixture is then extracted with water, dried over MgSO4 and evaporated down. The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate. There is obtained 2.0 g (8.2 mmol =42%) of the title compound as a colorless solid (mp=98° C.). The reaction mixture is then extracted with water dried over MgSO4 evaporated down The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 350 g (purity about 80%; 2.3 mol; prepared by a similar method to Bamberger et al., Ann. Chem. 316 (1901), 278) of N-(2-methylphenyl)hydroxylamine and 286.8 g (3.4 mol) of NaHCO3 in 700 ml of CH2Cl2 is treated with 447 g (2.85 mol) of phenyl chloroformate with vigorous stirring at about -10° C. The mixture is stirred for about 1 hour at -10° C. and 600 ml of water are then added dropwise, the temperature of the reaction mixture increasing to 5°-10° C. and a vigorous evolution of gas occurring. The aqueous phase is then separated off and extracted once more with CH2Cl2. The combined organic phases are extracted with water, dried over MgSO4 and concentrated. The residue crystallizes and is stirred with cyclohexane. 407 g (72%) of the title compound are obtained as a colorless solid. A mixture of 350 g (purity about 80% prepared by a similar method to Bamberger et al., Ann The mixture is stirred for about 1 hour at -10° C. the temperature of the reaction mixture increasing to 5°-10° C. The aqueous phase is then separated off extracted once more with CH2Cl2 The combined organic phases are extracted with water dried over MgSO4 concentrated The residue crystallizes is stirred with cyclohexane

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 350 g (purity about 80%; 2.3 mol; prepared by a similar method to Bamberger et al., Ann. Chem. 316 (1901), 278) of N-(2-methylphenyl)hydroxylamine and 286.8 g (3.4 mol) of NaHCO3 in 700 ml of CH2Cl2 is treated with 447 g (2.85 mol) of phenyl chloroformate with vigorous stirring at about -10° C. The mixture is stirred for about 1 hour at -10° C. and 600 ml of water are then added dropwise, the temperature of the reaction mixture increasing to 5°-10° C. and a vigorous evolution of gas occurring. The aqueous phase is then separated off and extracted once more with CH2Cl2. The combined organic phases are extracted with water, dried over MgSO4 and concentrated. The residue crystallizes and is stirred with cyclohexane. 407 g (72%) of the title compound are obtained as a colorless solid. A mixture of 350 g (purity about 80% prepared by a similar method to Bamberger et al., Ann The mixture is stirred for about 1 hour at -10° C. the temperature of the reaction mixture increasing to 5°-10° C. The aqueous phase is then separated off extracted once more with CH2Cl2 The combined organic phases are extracted with water dried over MgSO4 concentrated The residue crystallizes is stirred with cyclohexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 250 ml 3-neck RBF, stirring under nitrogen atmosphere, was charged 16.1 g (1.0 eq., 0.13 moles) N-2-methylphenylhydroxyamine in 40 ml methylene chloride and 16.8 g (1.5 eq., 0.20 moles) sodium bicarbonate neat. With a pipet added 13.1 g (1.05 eq, 0.37 moles) methyl chloroformate neat to the mixture at -5° C. to +5° C. The reaction mixture was stirred at 0° C. for 30 min. following the addition and the reaction was monitored by GC. The reaction mixture was stirred at 0° C. for 30 min. the addition

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The 2-N(OZ)CO2CH3 -benzylbromide, methyl N-(2-bromomethylphenyl)-N-alkoxycarbamate, is prepared as described in both EP619301 and EP704430 in a 4 step sequence as shown in scheme B. As described in the aforementioned European patent applications o-nitrotoluene is reacted with ammonium chloride in the presence of zinc to provide N-2-methyl phenyl hydroxylamine (XI) as described in Organic Synthesis Collective Volume III, p.668. The hydroxylamine is acylated with methyl chloroformate to provide the methyl phenyl N-hydroxycarbamate (XII) which is alkylated, for example with dimethylsulfate (R is methyl), to provide (XIII) which is brominated under standard conditions such as N-bromosuccinimide in carbon tetrachloride in the presence of a catalyst such as benzoyl peroxide to afford the intermediate benzylbromide (XIV). ##STR9##

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2.5 g (20 mmol) of N-(2-methylphenyl)-hydroxylamine (crude product, obtained according to Bamberger et al., Anm. Chem. 316 (1901), 278), 3.5 g (25 mmol) of K2CO3 and 3.5 g (22 mmol) of phenyl Chlorooformate in 20 ml of CH2Cl2 is stirred for 2 hours at room temperature. The reaction mixture is then extracted with water, dried over MgSO4 and evaporated down. The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate. There is obtained 2.0 g (8.2 mmol=42%) of the title compound as a colorless solid (mp=98° C.). The reaction mixture is then extracted with water dried over MgSO4 evaporated down The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2.5 g (20 mmol) of N-(2-methylphenyl)-hydroxylamine (crude product, obtained according to Bamberger et al., Anm. Chem. 316 (1901), 278), 3.5 g (25 mmol) of K2CO3 and 3.5 g (22 mmol) of phenyl Chlorooformate in 20 ml of CH2Cl2 is stirred for 2 hours at room temperature. The reaction mixture is then extracted with water, dried over MgSO4 and evaporated down. The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate. There is obtained 2.0 g (8.2 mmol=42%) of the title compound as a colorless solid (mp=98° C.). The reaction mixture is then extracted with water dried over MgSO4 evaporated down The residue is purified by column chromatography with mixtures of cyclohexane and ethyl acetate