반응 #57466

반응 방정식

(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

수율 86.4%

용매

acetonitrile

반응 조건

후처리

1. 1
   기타the reaction mixture was evaporated in vacuo
2. 2
   기타partitioned between ethyl acetate and aqueous potassium carbonate (5% w/v)
3. 3
   기타The layers were separated
4. 4
   추출the aqueous layer was back extracted with ethyl acetate
5. 5
   세척The combined organic layers were washed twice with 1N sodium hydrogen sulfate
6. 6
   추출back extracted with ethyl acetate
7. 7
   세척The combined organic layers were washed with brine
8. 8
   건조dried over anhydrous magnesium sulfate
9. 9
   여과filtered
10. 10
    기타evaporated in vacuo
11. 11
    기타The residue was purified on a preparative TLC plate (20×20 cm, 1000 μM)
12. 12
    세척eluting with 93:7 dichloromethane
13. 13
    기타The product band was removed
14. 14
    세척eluted with 3:1 methylene chloride
15. 15
    여과methanol, filtered
16. 16
    기타evaporated in vacuo
17. 17
    기타The residue was crystallized with several drops of methanol
18. 18
    기타The residual solid was dried under high vacuum

실험 절차

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).

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