Diisopropylethylamine → (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[{[4-(benzyloxy)phenyl]sulfonyl}(cyclohexyloxy)amino]-2-hydroxypropylcarbamate

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A mixture of 4-benzyloxybenzenesulfonyl chloride (65 mg; 0.230 mmol), (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[(cyclohexyloxy)amino]-2-hydroxypropylcarbamate (100 mg, 0.230 mmol), diisoproylethylamine (0.042 mL, 0.242 mmol) and 4-dimethylaminopyridine (˜1 mg) in anhydrous tetrahydrofuran (3 mL) was stirred at ambient temperature under an Argon atmosphere for 16 hours. An additional quantity of 4-benzyloxybenzenesulfonyl chloride (13 mg, 0.046 mmol) and 4-dimethylaminopyridine (˜1 mg) was added and the reaction was heated at reflux for approximately 2 hours. After cooling to ambient temperature, the reaction mixture was partitioned between ethyl acetate and aqueous hydrochloric acid. The phases were separated and the organic layer was then washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The crude product was purified on flash grade silica gel eluting with 1:1 ethyl acetate:hexane. Fractions containing the product were combined and evaporated in vacuo and dried under high vacuum to provide (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[{[4-(benzyloxy)phenyl]sulfonyl}(cyclohexyloxy)amino]-2-hydroxypropylcarbamate (143 mg, 91%). H1-NMR (chloroform-D3): 1.27 (m, 6H), 1.61 (m, 5H), 2.07 (m, 2H), 2.91 (m, 4H), 3.10 (b, 1H), 3.68 (m, 2H), 3.89 (m, 4H), 4.19 (m, 1H), 4.84 (m, 1H), 5.01 (m, 1H), 5.12 (s, 2H), 5.64 (d, 1H), 7.05 (d, 2H), 7.28 (m, 10H), 7.71 (d, 2H). MS(ESI): 703(M+Na).

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