Hydrochloric Acid → (2R,4R)-1-allyloxycarbonyl-4-hydroxy-2-{2-(5-methoxymethylimidazol-1-yl)ethyl}pyrrolidine

To a solution of (2R,4R)-1-allyloxycarbonyl-4-t-butyldimethylsilyloxy-2-{2-(5-hydroxymethylimidazol-1-yl)ethyl}pyrrolidine (9.22 g) in tetrahydrofuran (100 ml) was added potassium t-butoxide (3.54 g) with stirring under ice-cooling and then added dropwise methyl iodide (2.80 ml) at the same condition. The mixture was stirred at the same temperature for 1 hour. Ethyl acetate (100 ml) was added to a reaction mixture. The solution was washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated in vacuo. The resulting residue was chromatographed on silica gel (200 g) eluting with a mixture of chloroform and methanol (19:1, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give a residue. To a solution of the residue (7.79 g) in methanol (100 ml) was added conc. hydrochloric acid (4.60 ml) with stirring at ambient temperature. The mixture was allowed to stand overnight. To the solution was added 28% sodium methoxide-methanol solution (10.6 ml) with stirring under ice-cooling. The resulting precipitates were filtered off and the filtrate was evaporated in vacuo to give a residue. The residue was chromatographed on silica gel (200 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 (2R,4R)-1-allyloxycarbonyl-4-hydroxy-2-{2-(5-methoxymethylimidazol-1-yl) ethyl}pyrrolidine (3.63 g).

1. temperaturecooling
2. stirringThe mixture was stirred at the same temperature for 1 hour
3. washThe solution was washed successively with water and saturated aqueous sodium chloride
4. dry with materialdried over anhydrous magnesium sulfate
5. customevaporated in vacuo
6. customThe resulting residue was chromatographed on silica gel (200 g)
7. washeluting with a mixture of chloroform and methanol (19:1, V/V)
8. additionThe fractions containing the desired compound
9. customwere collected
10. customevaporated in vacuo
11. customto give a residue
12. stirringwith stirring at ambient temperature
13. stirringwith stirring under ice-
14. temperaturecooling
15. customThe resulting precipitates
16. filtrationwere filtered off
17. customthe filtrate was evaporated in vacuo
18. customto give a residue
19. customThe residue was chromatographed on silica gel (200 g)
20. washeluting with a mixture of chloroform and methanol (9:1, V/V)
21. additionThe fractions containing the desired compound
22. customwere collected
23. customevaporated in vacuo

ORDレコード

ord-31b637a7161644ae8002f5951d2718e3

出典データセット

uspto-grants-1997_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05608056