反应详情

3-Bromoaniline (1.4 g, 8.1 mmol) was dissolved in diethyl ether (50 mL) and 3.5 M dry HCl in ethyl acetate (2.3 mL) was added. The mixture was concentrated in vacuo. The residue was added toluene (100 mL) and concentrated in vacuo. The residue was added toluene (100 mL) and diphosgene (8.1 g, 41 mmol) and the resulting mixture was refluxed for 1.5 hour. After cooling, the mixture was concentrated in vacuo. The residue was dissolved in toluene (100 mL) and concentrated in vacuo. The residue was dissolved in DMF (30 mL) and 4-[(4-cyclohexylphenylamino)methyl]benzoic acid (1.3 g, 4.1 mmol) was added. The mixture was stirred at room temperature for 16 hours. The mixture was added ethyl acetate (150 mL) and washed with water:brine (1:1) (2×100 mL). The organic phase was dried with sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting first with a mixture of ethyl acetate:n-heptane:triethylamine (7:2:1), then with ethyl acetate and finally with methanol to afford 1.95 g (94%) of 4-[3-(3-bromophenyl)-1-(4-cyclohexylphenyl)ureidomethyl]benzoic acid.

1. concentrationThe mixture was concentrated in vacuo
2. additionThe residue was added toluene (100 mL)
3. concentrationconcentrated in vacuo
4. temperaturethe resulting mixture was refluxed for 1.5 hour
5. temperatureAfter cooling
6. concentrationthe mixture was concentrated in vacuo
7. dissolutionThe residue was dissolved in toluene (100 mL)
8. concentrationconcentrated in vacuo
9. dissolutionThe residue was dissolved in DMF (30 mL)
10. washwashed with water:brine (1:1) (2×100 mL)
11. dry with materialThe organic phase was dried with sodium sulphate
12. concentrationconcentrated in vacuo
13. customThe residue was purified by column chromatography on silica gel eluting first with a mixture of ethyl acetate:n-heptane:triethylamine (7:2:1)