Sodium borohydride → (2S,4R)-2-(2-ureidoethyl)thiomethyl-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

To a solution of sodium borohydride (0.78 g) in tetrahydrofuran (25 ml) was added dropwise boron trifluoride dimethyl etherate (8.78 ml) with stirring under ice-cooling and the solution was stirred at the same temperature for 10 minutes. To this solution was added (2S,4R)-2-(carbamoylmethyl)thiomethyl-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (2.53 g) and the mixture was stirred at ambient temperature for 4 hours. To the reaction mixture was added methanol (5 ml) and the mixture was filtered. The filtrate was evaporated in vacuo to give a residue. The residue was dissolved in methanol (30 ml). To the solution was added 10% hydrogen chloride-methanol solution (10 ml) and the mixture was allowed to stand overnight at ambient temperature. The reaction mixture was evaporated in vacuo to give a residue. The residue was dissolved in a mixture of tetrahydrofuran (30 ml) and water (15 ml). To the solution was added a solution of potassium cyanate (3.83 g) in water (10 ml) and the mixture was stirred at 50°-60° C. for 30 minutes. The reaction mixture was evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of chloroform and methanol (9:1, v/v). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4R)-2-(2-ureidoethyl)thiomethyl-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.73 g).

1. temperaturecooling
2. stirringthe solution was stirred at the same temperature for 10 minutes
3. stirringthe mixture was stirred at ambient temperature for 4 hours
4. filtrationthe mixture was filtered
5. customThe filtrate was evaporated in vacuo
6. customto give a residue
7. customThe reaction mixture was evaporated in vacuo
8. customto give a residue
9. stirringthe mixture was stirred at 50°-60° C. for 30 minutes
10. customThe reaction mixture was evaporated in vacuo
11. customThe resulting residue was chromatographed on silica gel (100 g)
12. washeluting with a mixture of chloroform and methanol (9:1
13. additionThe fractions containing the desired compound
14. customwere collected
15. customevaporated in vacuo

ORD record

ord-a219bc91a1a947dcb060ce8f6741e110

Source dataset

uspto-grants-1991_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05061804