Ethylmorpholine → L-Proline 1,1-dimethylethyl ester

Temperature

-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 (2.134 mmol) 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 record

ord-abe305f85d7b41cbac2bbe29105a2ed8

Source dataset

uspto-grants-1996_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05554756