反应详情

温度

-10 °C

2.65 g of N-(benzyloxycarbonyl)-4(R)-hydroxy-L-proline were dissolved in 10 ml of dry tetrahydrofuran and cooled to -10° C. while stirring with a magnetic stirrer. 1.15 g of N-ethylmorpholine were added followed immediately by 1.36 g of isobutyl chloroformate. The mixture was stirred at -10° C. for 30 minutes and then 2.19 g of tert.butylamine were added. Stirring was continued at -10° C. for 1 hour, the mixture was allowed to warm to room temperature during 2 hours and was then left to stand for 2 hours. The solvent was removed by evaporation in a vacuum and the residue was partitioned between ethyl acetate and water. The organic layer was washed with 10% citric acid solution and sodium bicarbonate solution and then dried over sodium sulphate. The solvent was removed by evaporation to give a solid which was triturated with diethyl ether and filtered off. There were obtained 2.23 g of crude product which was recrystallized from ethyl acetate/diethyl ether to give 1.57 g of N2 (benzyloxycarbonyl)-N1 tert.butyl-4(R)-hydroxy-L-prolinamide of melting point 128°-130° C.

1. stirringThe mixture was stirred at -10° C. for 30 minutes
2. stirringStirring
3. temperatureto warm to room temperature during 2 hours
4. waitwas then left
5. waitto stand for 2 hours
6. customThe solvent was removed by evaporation in a vacuum
7. customthe residue was partitioned between ethyl acetate and water
8. washThe organic layer was washed with 10% citric acid solution and sodium bicarbonate solution
9. dry with materialdried over sodium sulphate
10. customThe solvent was removed by evaporation
11. customto give a solid which
12. customwas triturated with diethyl ether
13. filtrationfiltered off
14. customThere were obtained 2.23 g of crude product which
15. customwas recrystallized from ethyl acetate/diethyl ether