Diisopropylamine → dimethyl (R)-N-tert-butoxycarbonyl-3-propionylaspartate

A solution of 2.61 g (10 m mol) of dimethyl (R)-N-tert-butoxycarbonylaspartate in 10 ml of tetrahydrofuran was added dropwise to a lithium isopropylamide solution [prepared from 4.62 ml (33 m mol) of diisopropylamine and 21 ml (33 m mol) of butyllithium hexane solution, in 30 ml of tetrahydrofuran]at -78° C. in a stream of nitrogen. The mixture was stirred for 10 minutes and a solution of 2.48 g (20 m mol) of propionylimidazole in 15 ml of tetrahydrofuran was added dropwise. The reaction mixture was stirred for 10 minutes at -78° C. and further stirred in a dry ice-acetone bath of -40° C. Stirring was continued until the temperature of the mixture reached -20° C. Then a saturated ammonium chloride aqueous solution was added and the mixture was stirred at room temperature. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over anhydrous sodium sulfate and distilled under reduced pressure. The residue was subjected to a silica gel column (2.5×40 cm) chromatography (ethyl acetate:hexane=1:3→1:2) to obtain 2.93 g (92%) of dimethyl (R)-N-tert-butoxycarbonyl-3-propionylaspartate as colorless oil.

1. stirringThe reaction mixture was stirred for 10 minutes at -78° C.
2. stirringfurther stirred in a dry ice-acetone bath of -40° C
3. stirringStirring
4. customreached -20° C
5. stirringthe mixture was stirred at room temperature
6. extractionextracted with ethyl acetate
7. washThe organic layer was washed with a saturated saline solution
8. dry with materialdried over anhydrous sodium sulfate
9. distillationdistilled under reduced pressure

ORD record

ord-a8ba874b714c45f5968db3fed02a600d

Source dataset

uspto-grants-1991_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05021439