反应详情

Lithium hydroxide monohydrate (4.0 equiv.) in water (0.66 M) was added to a stirred mixture of (R)-methyl 5-(2-benzyl-6-((1-(4-fluorophenyl)ethyl)carbamoyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (1 eq) in MeOH/THF (v/v=1/4) and the mixture was stirred at room temperature. After 2 h, the mixture was neutralized with 1 N HCl, extracted with EtOAc, dried over Na2SO4, filtered and evaporated to dryness. To the residue was added Et2O and sonicated, upon which some solid precipitated. The solids were filtered, triturated with Et2O and dried to yield (R)-5-(2-benzyl-6-((1-(4-fluorophenyl)ethyl)carbamoyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acid. LCMS [M+H]+=501. 1H NMR (CDCl3, 500 MHz) δ ppm: 8.44 (d, 1H, J=8.5 Hz), 7.92 (br s, 1H), 7.71 (d, 1H, J=8.0 Hz), 7.40 (dd, 2H, J=5.0 Hz, J=8.5 Hz), 7.32-7.23 (m, 3H), 7.12 (d, 2H, J=7.5 Hz), 7.06 (t, 2H, J=9.0 Hz), 6.42 (s, 1H), 5.43 (br s, 2H), 5.39-5.35 (m, 1H), 2.63 (t, 2H, J=7.5 Hz), 2.37 (t, 2H, J=6.5 Hz), 1.70-1.64 (m, 4H), 1.63 (d, 3H, J=7.0 Hz).

1. extractionextracted with EtOAc
2. dry with materialdried over Na2SO4
3. filtrationfiltered
4. customevaporated to dryness
5. additionTo the residue was added Et2O
6. customsonicated, upon which some solid
7. customprecipitated
8. filtrationThe solids were filtered
9. customtriturated with Et2O
10. customdried