反应详情

A slurry of the compound of Intermediate 1 (51.2 g, 0.267 mol) in DCM (195 ml) and thionyl chloride (195 ml, 2.67 mol) was treated with DMF (5 drops) and heated to reflux for 4 h. The reaction was concentrated in vacuo and azeotroped with toluene (2×50 ml) to give a yellow solid which was used without further purification. A solution of ethyl-(S)-3-(4-aminophenyl)-2-(t-butoxycarbonylamino)propanoate (130.8 g, 0.425 mol) in DCM (800 ml) was cooled to 0° and treated with NMM (56.0 ml, 0.51 mol), stirred for 5 minutes and then a solution of the acid chloride (98.3 g, 0.468 mol) in DCM (200 ml) was added dropwise keeping the reaction temperature below 5°. The reaction was stirred for 1 h, quenched with NaHCO3 solution (500 ml), the organic layer separated, washed with NaHCO3 solution (500 ml), 10% citric acid solution (500 ml) and NaHCO3 solution (500 ml), dried (MgSO4) and concentrated in vacuo to give a yellow solid which was recrystallised (EtOAc/hexane) to give the title compound, (140 g, 69%). δH (DMSO d6), 8.8 (2H, s), 7.55 (2H, d, J 8.5 Hz), 7.23 (2H, d, J 8.5 Hz), 4.0 (3H, m), 3.4 (2H, b s), 2.9 (1H, m), 2.8 (1H, m), 1.3 (9H, s), 1.25 (3H, t); m/z (ES+, 70V) 504 (MNa+).

1. temperatureheated
2. temperatureto reflux for 4 h
3. concentrationThe reaction was concentrated in vacuo
4. customazeotroped with toluene (2×50 ml)
5. customto give a yellow solid which
6. customwas used without further purification
7. customthe reaction temperature below 5°
8. stirringThe reaction was stirred for 1 h
9. customquenched with NaHCO3 solution (500 ml)
10. customthe organic layer separated
11. washwashed with NaHCO3 solution (500 ml), 10% citric acid solution (500 ml) and NaHCO3 solution (500 ml)
12. dry with materialdried (MgSO4)
13. concentrationconcentrated in vacuo
14. customto give a yellow solid which
15. customwas recrystallised (EtOAc/hexane)