Hydrochloric Acid → Methyl (2S)-2-({2-[(tert-butoxycarbonyl)amino]ethyl}amino)-3-(1H-imidazol-4-yl)propanoate

L-Histidine methyl ester (7.93 g, 32.8 mmol) and sodium acetate (10.75 g, 131 mmol) were added to a stirred solution of tert-butyl N-(2-oxoethyl)carbamate (5.22 g, 32.8 mmol) in methanol (100 ml). 4 Å molecular sieves and sodium cyanoborohydride (4.12 g, 65.6 mmol) were added and the mixture was stirred at room temperature for 17 hours. Aqueous hydrochloric acid (2N, 4 ml) was added and the mixture was then basified with saturated aqueous sodium carbonate solution to pH=10. The mixture was filtered to remove solid which was washed with methanol. Methanol was removed by evaporation under reduced pressure and the residual aqueous solution was extracted with ethyl acetate (2×300 ml). The combined organic extracts were then dried (MgSO4), filtered, and concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel, eluting with a solvent gradient of dichloromethane:methanol (96:4 to 92:8), to afford the title compound as a colorless oil, 8.07 g, 79% yield.

1. filtrationThe mixture was filtered
2. customto remove solid which
3. washwas washed with methanol
4. customMethanol was removed by evaporation under reduced pressure
5. extractionthe residual aqueous solution was extracted with ethyl acetate (2×300 ml)
6. dry with materialThe combined organic extracts were then dried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe resultant residue was purified by column chromatography on silica gel
10. washeluting with a solvent gradient of dichloromethane:methanol (96:4 to 92:8)

ORD record

ord-d32c5c04ec1f4be7978cd3cf53678716

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06949577B2