Water → tert-Butyl {(1S,2R)-1-benzyl-2-hydroxy-3-[(5-methyl-1H-imidazol-2-yl)amino]-3-oxopropyl}carbamate

To a 5.00 ml solution of benzyl 2-amino-4-methyl-1H-imidazole-1-carboxylate obtained in Reference Example 32 601 mg (2.60 mmol), (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-4-phenylbutanoic acid 590 mg (2.00 mmol) and HOBt.H2O 321 mg (2.10 mmol) in DMF was added WSC.HCl 422 mg (2.20 mmol) and the mixture was stirred at room temperature for 5 hours. After distillating DMF off, the mixture was extracted by adding ethyl acetate and 5% aqueous sodium carbonate solution. The organic layer was washed with an aqueous saturated sodium chloride solution and dried on sodium sulfate. Filtration and concentration gave a residue and the resulting residue was redissolved in methanol 30 mL. To this solution were added ammonium formate 2.52 g (40.00 mmol), 10% Pd/C (containing 50% water) and the mixture was heated under reflux for 2 hours. The mixture was filtered to remove 10% Pd/C and concentrated. The concentrated residue was suspended in ethyl acetate and washed with 5% sodium carbonate and an aqueous saturated sodium chloride solution. The organic layer was dried on sodium sulfate. After filtration and concentration of the mixture, the mixture was purified by a column chromatography on silica gel (eluted with a mixed solvent of chloroform and methanol) to give 558 mg (1.49 mmol) of the title compound (yield: 75%).

1. extractionwas extracted
2. additionby adding ethyl acetate and 5% aqueous sodium carbonate solution
3. washThe organic layer was washed with an aqueous saturated sodium chloride solution
4. customdried on sodium sulfate
5. filtrationFiltration and concentration
6. customgave a residue
7. temperaturethe mixture was heated
8. temperatureunder reflux for 2 hours
9. filtrationThe mixture was filtered
10. customto remove 10% Pd/C
11. concentrationconcentrated
12. washwashed with 5% sodium carbonate
13. customThe organic layer was dried on sodium sulfate
14. filtrationAfter filtration and concentration of the mixture
15. customthe mixture was purified by a column chromatography on silica gel (
16. washeluted with a mixed solvent of chloroform and methanol)

ORD record

ord-638d78198fd046e0b2fe14ef5d0d9443

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07816387B2