反应详情

To a solution of N1-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N1-(cyclopentyloxy)-4-methoxy-1-benzenesulfonamide×trifluoracetic acid (Step 1, Example 48), (50 mg, 0.091 mmol) in approximately 1.5 mL of dichloromethane under Argon was added benzylchloroformate (15.6 μL, 0.109 mmol) followed by N,N-diisopropylethylamine (47.9 μL, 0.273 mmol). After stirring 18 hours, the reaction mixture was evaporated in vacuo to a residue and purified on a preparative silica gel TLC plate (20×20 cm, 1000 μM) eluting with 95:5 methylene chloride:methanol. The product band was removed, eluted with 4:1 methylene chloride:methanol, filtered, and evaporated in vacuo. The residue was partitioned between dichloromethane and water. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was lyophilized from acetonitrile and water to provide phenylmethyl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate (37 mg, 71%). H1-NMR (methanol-D4) 1.71 (m, 8H), 2.59 (m, 1H), 2.93 (m, 2H), 3.10 (m, 1H), 3.81 (m, 2H), 3.83 (s, 3H), 4.86 (m, 3H), 7.06 (m, 2H), 7.21 (m, 10H), 7.73 (m, 2H). MS(ESI): 591 (M+Na).

1. customthe reaction mixture was evaporated in vacuo to a residue
2. custompurified on a preparative silica gel TLC plate (20×20 cm, 1000 μM)
3. washeluting with 95:5 methylene chloride
4. customThe product band was removed
5. washeluted with 4:1 methylene chloride
6. filtrationmethanol, filtered
7. customevaporated in vacuo
8. customThe residue was partitioned between dichloromethane and water
9. customThe organic layer was separated
10. dry with materialdried over anhydrous magnesium sulfate
11. filtrationfiltered
12. customevaporated in vacuo