methyl N-(4-bromo-3-fluorophenyl)carbamate

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

実験手順: The title compound, m.p. 121–122° C., was prepared in accordance with the general method of example 81a) from 4-bromo-3-fluoroaniline and methyl chloroformate.

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

実験手順: The title compound, m.p. 121-122° C., was prepared in accordance with the general method of example 81a) from 4-bromo-3-fluoroaniline and methyl chloroformate.

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

実験手順: To 33.3 g (0.3 mol) 3-fluoroaniline in 160 ml CH2Cl2 were added 450 ml of a 0.7 M aqueous NaHCO3-solution. The resulting mixture was treated dropwise with 34.6 ml (0.41 mol) methylchloroformate within a period of 20 min. After stirring overnight the layers were separated and the organic layer was washed with saturated aqueous NaCl and dried with MgSO4. After evaporation of ca.60% of the solvent, 600 ml of hexane were added, whereby (3-Fluoro-phenyl)-carbamic acid methyl ester precipitated as a colorless solid that was filtered off and dried i.v (41 g (81%)). The solid was dissolved in 600 ml acetonitrile and treated subsequently with 50 g (0.28 mmol) N-bromosuccinimide and 2.13 ml (0.024 mol) trifluormethane sulfonic acid. After stirring at room temperature during 12 hours ca 50% of the solvent were evaporated, the resulting mixture diluted with 1000 ml EtOAc, and washed subsequently with saturated aqueous NaHCO3 and saturated aqueous NaCl. Drying of the combined organic layers with MgSO4, evaporation of the solvent, and column chromatography on silica gel with hexane/EtOAc 8:1 and then 2:1 gave 39 g (64%) (4-Bromo-3-fluoro-phenyl)-carbamic acid methyl ester as a colorless solid, that was dissolved in 390 ml acetonitrile, treated subsequently with 39 g (0.172 mol) N-iodosuccinimide and 1.4 ml (0.016 mol) trifluormethanesulfonic acid at 0° C. and left to stirr at room temperature during 10 hours. Cooling the reaction mixture to 0° C. led to precipitation of (4-Bromo-5-fluoro-2-iodo-phenyl)-carbamic acid methyl ester as colorless crystals that were filtered off and dried (26.7g, 44%). Dilution of the filtrate with 600 ml hexane followed by subsequent washing with saturated aqueous NaHCO3 and 0.5M aqueous NaS2O3, drying of the organic layer with MgSO4, evaporation of the solvent, and recrystallization of the residue in acetonitrile gave an additional 6.3 g (12%) of (4-Bromo-5-fluoro-2-iodo-phenyl)-carbamic acid methyl ester (total: 33 g, 56%), MS: 373 (M, 1Br). were separated the organic layer was washed with saturated aqueous NaCl dried with MgSO4 After evaporation of ca 60% of the solvent, 600 ml of hexane were added whereby (3-Fluoro-phenyl)-carbamic acid methyl ester precipitated as a colorless solid that was filtered off dried i.v (41 g (81%)) The solid was dissolved in 600 ml acetonitrile were evaporated the resulting mixture diluted with 1000 ml EtOAc washed subsequently with saturated aqueous NaHCO3 and saturated aqueous NaCl Drying of the combined organic layers with MgSO4, evaporation of the solvent, and column chromatography on silica gel with hexane/EtOAc 8:1

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

実験手順: The title compound, m.p. 121-122° C., was prepared in accordance with the general method of example 26g) from 4-bromo-3-fluoroaniline and methyl chloroformate.

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

実験手順: The title compound, m.p. 121–122° C., was prepared in accordance with the general method of example 81a) from 4-bromo-3-fluoroaniline and methyl chloroformate.

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

実験手順: The title compound, m.p. 121-122° C., was prepared in accordance with the general method of example 81a) from 4-bromo-3-fluoroaniline and methyl chloroformate.