反应详情

(2S,5R)-2-(((1r*,3R*,4R*)-3-(tert-butyldimethylsilyloxy)-4-fluorocyclopentyl)methyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (500 mg, 1.21 mmol) was dissolved in 1:1 mixture of 1 N HCl solution and acetonitrile (50 mL). The mixture was stirred 3 h at rt, then concentrated. K2CO3 (840 mg, 5 equiv.) and CbzOSu (903 mg, 3 equiv.) were added to the residue, The mixture was dissolved in 1:1 water and acetonitrile (50 mL), stirred overnight at rt. The acetonitrile was removed by evaporation under reduced pressure. The aqueous residue was extracted by EtOAc (3×20 mL). The combined organic layers were washed by brine (20 mL), dried over Na2SO4. After filtration and concentration, the residue was purified by ISCO (40 g column) to afford 274 mg (67% yield) of (s)-methyl 2-(benzyloxycarbonylamino)-3-((1r*,3R*,4R*)-3-fluoro-4-hydroxycyclopentyl)propanoate. MS ESI +ve m/z 362 (M+Na). 1H NMR (CDCl3) δ 7.35 (m, 5H), 5.34 (s, 1H), 5.10 (s, 2H), 4.82 (d, 1H), 4.39-4.19 (m, 2H), 3.73 (s, 3H), 2.43-2.24 (m, 2H), 2.09-1.38 (m, 6H). 19F NMR (CDCl3) δ −175.92.

1. concentrationconcentrated
2. stirringstirred overnight at rt
3. customThe acetonitrile was removed by evaporation under reduced pressure
4. extractionThe aqueous residue was extracted by EtOAc (3×20 mL)
5. washThe combined organic layers were washed by brine (20 mL)
6. dry with materialdried over Na2SO4
7. filtrationAfter filtration and concentration
8. customthe residue was purified by ISCO (40 g column)