تفاعل #57466

معادلة التفاعل

(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

المردود 86.4%

المذيبات

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىthe reaction mixture was evaporated in vacuo
2. 2
   أخرىpartitioned between ethyl acetate and aqueous potassium carbonate (5% w/v)
3. 3
   أخرىThe layers were separated
4. 4
   استخلاصthe aqueous layer was back extracted with ethyl acetate
5. 5
   غسيلThe combined organic layers were washed twice with 1N sodium hydrogen sulfate
6. 6
   استخلاصback extracted with ethyl acetate
7. 7
   غسيلThe combined organic layers were washed with brine
8. 8
   تجفيفdried over anhydrous magnesium sulfate
9. 9
   ترشيحfiltered
10. 10
    أخرىevaporated in vacuo
11. 11
    أخرىThe residue was purified on a preparative TLC plate (20×20 cm, 1000 μM)
12. 12
    غسيلeluting with 93:7 dichloromethane
13. 13
    أخرىThe product band was removed
14. 14
    غسيلeluted with 3:1 methylene chloride
15. 15
    ترشيحmethanol, filtered
16. 16
    أخرىevaporated in vacuo
17. 17
    أخرىThe residue was crystallized with several drops of methanol
18. 18
    أخرىThe residual solid was dried under high vacuum

الإجراء التجريبي

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).

المصدر