Reaktion #158028

Reaktionsgleichung

(R)-4-(4-ethoxy-1-(5′-fluoro-2′-methoxybiphenyl-4-yl)-4-oxobutan-2-ylannino)-4-oxobutanoic acid

NaOH

→

(R)-4-(1-carboxy-3-(5′-fluoro-2′-methoxybiphenyl-4-yl)propan-2-ylamino)-4-oxobutanoic acid

Ausbeute 74.9%

Lösungsmittel

MeOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenthe crude is concentrated under reduced pressure
2. 2
   Sonstigeto remove MeOH
3. 3
   workup.ADDITIONis diluted with EtOAc
4. 4
   WaschenThe organic layer is washed with brine
5. 5
   Trocknendried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated under reduced pressure
8. 8
   SonstigeThe obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)

Vorschrift

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)

Quelle