Ethylmorpholine → L-Proline 1,1-dimethylethyl ester

Temperatur

-15 °C

0.566 g (2.134 mmol) of N-(benzyloxycarbonyl)-L-leucine was taken up in 15 ml of tetrahydrofuran and cooled to -15° C. 0.245 g (2.134 mmol) of N-ethylmorpholine and 0.291 g (2.134mmol) of isobutyl chloroformate were added. After 5 minutes the tetrahydrofuran solution prepared as described in the previous paragraph was added, followed by 0.451 g (4.27 mmol) of N-ethylmorpholine. The mixture was stirred at room temperature for 10 hours, the solvent was then removed by evaporation and the residue was partitioned between ethyl acetate and water. The ethyl acetate solution was washed with saturated sodium bicarbonate solution and with saturated sodium chloride solution and then dried over anhydrous sodium sulphate. The solvent was removed under a vacuum to give 1.5 g of crude N-[3(S)-[[N-(benzyloxycarbonyl)-L-leucyl]amino]-2-(R and S)-hydroxy-4-phenylbutyl]-L-proline tert.butyl ester as an oil. The two isomers were separated by chromatography on silica gel using 50% n-hexane in ethyl acetate for the elution. There were obtained 180 mg of isomer 1 of N-[3(S)-[[N-(benzyloxycarbonyl)-L-leucyl]amino]-2(R or S)-hydroxy-4-phenylbutyl]-L-proline tert.butyl ester as a crystalline material; Rf (System A): 0.34; MS: m/e 582 [M+H]+, and 70 mg of isomer 2 as a crystalline material; Rf (System A): 0.28; MS: m/e 582 [M+H]+.

1. additionwas added
2. customthe solvent was then removed by evaporation
3. customthe residue was partitioned between ethyl acetate and water
4. washThe ethyl acetate solution was washed with saturated sodium bicarbonate solution and with saturated sodium chloride solution
5. dry with materialdried over anhydrous sodium sulphate
6. customThe solvent was removed under a vacuum

ORD-Eintrag

ord-fa00b1b67f064d65bdc503f2fea43ad1

Quelldatensatz

uspto-grants-1997_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05620987