反应详情

To a solution of (R)-4-(4-ethoxy-1-(5′-fluoro-2′-methoxybiphenyl-4-yl)-4-oxobutan-2-ylannino)-4-oxobutanoic acid (83 mg, 0.192 mmol) in MeOH (2 mL) is added 1N NaOH (4 mL, 4 mmol) After stirring at room temperature for 2 hours, the crude is concentrated under reduced pressure to remove MeOH and is diluted with EtOAc. The organic layer is washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN), and then lyophilized to give (R)-4-(1-carboxy-3-(5′-fluoro-2′-methoxybiphenyl-4-yl)propan-2-ylamino)-4-oxobutanoic acid (58 mg). HPLC retention time=1.46 minutes (condition D); MS (m+1)=404.2; 1H NMR (400 MHz, CD3OD) δ ppm 2.36-2.59 (m, 6 H) 2.84 (dd, J=13.4, 6.3 Hz, 1 H) 2.91 (dd, J=13.4, 6.3 Hz, 1 H) 3.75 (s, 3 H) 4.34-4.56 (m, 1 H) 6.95-7.08 (m, 3 H) 7.26 (d, J=8.1 Hz, 2 H) 7.42 (d, J=8.3 Hz, 2 H)

1. concentrationthe crude is concentrated under reduced pressure
2. customto remove MeOH
3. additionis diluted with EtOAc
4. washThe organic layer is washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)