Reaktion #57466

Reaktionsgleichung

(3R,4S)-4-amino-1-(cyclopentyloxy)-5-phenyl-1-(6-quinoxalinylsulfonyl)-3-pentanol

2,5-dioxo-1-pyrrolidinyl [(3S)tetrahydro-3-furanyl] carbonate

N,N-diisopropylethylamine

→

(3S)tetrahydro-3-furanyl N-[(1S,2R)-1-benzyl-4-(cyclopentyloxy)-2-hydroxy-4-(6-quinoxalinyl sulfonyl)butyl]carbamate

Ausbeute 86.4%

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe reaction mixture was evaporated in vacuo
2. 2
   Sonstigepartitioned between ethyl acetate and aqueous potassium carbonate (5% w/v)
3. 3
   SonstigeThe layers were separated
4. 4
   Extraktionthe aqueous layer was back extracted with ethyl acetate
5. 5
   WaschenThe combined organic layers were washed twice with 1N sodium hydrogen sulfate
6. 6
   Extraktionback extracted with ethyl acetate
7. 7
   WaschenThe combined organic layers were washed with brine
8. 8
   Trocknendried over anhydrous magnesium sulfate
9. 9
   Filtrationfiltered
10. 10
    Sonstigeevaporated in vacuo
11. 11
    SonstigeThe residue was purified on a preparative TLC plate (20×20 cm, 1000 μM)
12. 12
    Wascheneluting with 93:7 dichloromethane
13. 13
    SonstigeThe product band was removed
14. 14
    Wascheneluted with 3:1 methylene chloride
15. 15
    Filtrationmethanol, filtered
16. 16
    Sonstigeevaporated in vacuo
17. 17
    SonstigeThe residue was crystallized with several drops of methanol
18. 18
    SonstigeThe residual solid was dried under high vacuum

Vorschrift

A mixture of (3R,4S)-4-amino-1-(cyclopentyloxy)-5-phenyl-1-(6-quinoxalinylsulfonyl)-3-pentanol (50 mg, 0.110 mmoL), 2,5-dioxo-1-pyrrolidinyl [(3S)tetrahydro-3-furanyl] carbonate (28 mg, 0.121 mmol, WO 94/05639) and N,N-diisopropylethylamine (47.8 μL, 0.274 mmol) were combined under Argon at ambient temperature in approximately 1.5 mL of acetonitrile. After stirring for approximately 16 hours at ambient temperature, the reaction mixture was evaporated in vacuo and partitioned between ethyl acetate and aqueous potassium carbonate (5% w/v). The layers were separated and the aqueous layer was back extracted with ethyl acetate. The combined organic layers were washed twice with 1N sodium hydrogen sulfate. The acid layers were combined and back extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on a preparative TLC plate (20×20 cm, 1000 μM) eluting with 93:7 dichloromethane:methanol. The product band was removed, eluted with 3:1 methylene chloride:methanol, filtered, and evaporated in vacuo. The residue was crystallized with several drops of methanol. The residual solid was dried under high vacuum to provide (3S)tetrahydro-3-furanyl N-[(1S,2R)-1-benzyl-4-(cyclopentyloxy)-2-hydroxy-4-(6-quinoxalinyl sulfonyl)butyl]carbamate (54 mg, 86%) as a white solid. H1-NMR (chloroform-D3): 1.61 (m, 5H), 1.86 (m, 4H), 2.09 (m, 1H), 2.97 (m, 3H), 3.20 (m, 2H), 3.80 (m, 6H), 4.83 (m, 1H), 4.93 (m, 1H), 5.14 (m, 1H), 7.28 (m, 5H), 8.13 (m, 1H), 8.31 (d, 1H), 8.69 (d, 1H), 9.05 (s, 2H). MS(ESI): 571(M+H).

Quelle