Hydrochloric Acid → (2S,4S)-2-(4-carbamoylpiperazin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)-4-(triphenylmethylthio)pyrrolidine

A mixture of (2S,4S)-2-(methanesulfonyloxy)methyl-1-(4-nitrobenzyloxycarbonyl)-4-(triphenylmethylthio)-pyrrolidine (2.28 g) and piperazine (0.93 g) in dimethylformamide (40 ml) was stirred at 80°-90° C. for 5 hours. The reaction mixture was poured into ice-water (150 ml). The precipitates were collected by filtration, washed with water and dissolved in ethyl acetate (100 ml). The solution was washed twice with saturated aqueous sodium chloride (30 ml), dried over anhydrous magnesium sulfate and evaporated in vacuo to give a residue. The residue was dissolved in a mixture of tetrahydrofuran (20 ml) and water (10 ml). To the solution were added conc. hydrochloric acid (0.60 ml) and potassium cyanate (0.44 g) and the mixture was stirred at 50° C. for 30 minutes. Ethyl acetate was added to the reaction mixture with stirring. The organic layer was separated and washed twice with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (2:1, V/V and then 1:2, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4S)-2-(4-carbamoylpiperazin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)-4-(triphenylmethylthio)pyrrolidine (1.30 g).

1. filtrationThe precipitates were collected by filtration
2. washwashed with water
3. dissolutiondissolved in ethyl acetate (100 ml)
4. washThe solution was washed twice with saturated aqueous sodium chloride (30 ml)
5. dry with materialdried over anhydrous magnesium sulfate
6. customevaporated in vacuo
7. customto give a residue
8. stirringthe mixture was stirred at 50° C. for 30 minutes
9. stirringwith stirring
10. customThe organic layer was separated
11. washwashed twice with saturated aqueous sodium chloride
12. dry with materialdried over anhydrous magnesium sulfate
13. customevaporated in vacuo
14. customThe resulting residue was chromatographed on silica gel (100 g)
15. washeluting with a mixture of dichloromethane and acetone (2:1, V/V
16. additionThe fractions containing the desired compound
17. customwere collected
18. customevaporated in vacuo

ORD 기록

ord-e65d683c6f544a97a39286942ae3172a

출처 데이터셋

uspto-grants-1993_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05202437