反应详情

温度

40 °C

To a suspension of 2-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-4-carboxylic acid (1165 g, 4.994 mol) in dichloromethane (10 L) was added O-tert-butyl-N,N′-diisopropylurea (3020 g, 15.00 mol) at room temperature with stirring, and the reaction system was cooled by adding ice water to outer bath when increase of inner temperature and start of the refluxing were noted. When the temperature decreased to room temperature, the reaction mixture was stirred for 1 hour after removing the ice bath, and for 3 hours by heating to 40° C. After stirring the reaction mixture in an ice bath for 1 hour, the insoluble content was separated by filtration, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography (silica gel, 4 kg; elution solution, hexane:ethyl acetate, 3:1) to obtain 925.2 g (64%) of a mixture of isomers at position 4 as a pale yellow syrup. Although separation of the isomers was easy, the isomers were used without separation since the subsequent step involved racemization. 1H-NMR spectrum of the isomers authentic sample is shown below.

1. temperaturethe reaction system was cooled
2. temperatureincrease of inner temperature and start of the refluxing
3. customdecreased to room temperature
4. stirringthe reaction mixture was stirred for 1 hour
5. customafter removing the ice bath
6. stirringAfter stirring the reaction mixture in an ice bath for 1 hour
7. customthe insoluble content was separated by filtration
8. customthe solvent was removed by distillation under reduced pressure
9. customThe residue was purified by silica gel column chromatography (silica gel, 4 kg; elution solution, hexane:ethyl acetate, 3:1)