反应详情

To a solution of 0.89 g (3 mmol) triphosgene in 10 ml CH2Cl2 was added a solution of 2.0 g (8 mmol) 4-aminobenzylamine, tertbutylcarbamate and 1.69 ml (9.7 mmol) diisopropylethylamine in 25 ml CH2Cl2 dropwise over 1 hour. After the addition was complete, a solution of 1.79 g (8 mmol) 2-isopropylamino-1-(3,4-dichlorophenyl)-ethanol and 1.69 ml (9.7 mmol) diisopropylethylamine in 25 ml CH2Cl2 was added over 5 min. The reaction mixture was stirred for 10 min. diluted with 200 ml EtOAc, washed with 200 ml each of saturated aqueous NaHCO3, water, and brine, then dried over Na2SO4 , filtered and concentrated. Purification by flash chromatography (50% EtOAc/hexanes) provided 4 g (4-{3-[2-(3,4-Dichloro-phenyl)-2-hydroxy-ethyl]-3-isopropyl-ureido}-benzyl)-carbamic acid tert-butyl ester. 1H NMR (300 mHz, CDCl3) 8.85 (br s, 1H); 7.45 (m, 2H); 7.3-7.0 (m, 5H); 5.82 (s, 1H); 5.12 (br s, 1H); 4.7 (d, 1H, J=8 Hz); 4.4-4.15 (m, 3H); 3.42 (dd, 1H, J=16 and 8 Hz); 3.1 (d, 1H, J=16 Hz); 1.4 (s, 9H); 1.9 (d, 3H, J=7 Hz); 1.07 (d, 3H, J=7 Hz).

1. additionAfter the addition
2. washwashed with 200 ml each of saturated aqueous NaHCO3, water, and brine
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customPurification by flash chromatography (50% EtOAc/hexanes)