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

Participants

Reaction Steps

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).

Provenance & Evidence