Sodium Hydroxide → (R)-4-(1-carboxy-3-(5'-fluoro-2'-methoxybiphenyl-4-yl)propan-2-ylamino)-4-oxobutanoic acid

HRID 70846Notes

Reaction equation

HRID 70846 reaction equation
C([O:3][C:4](=[O:31])[CH2:5][C@H:6]([NH:23][C:24](=[O:30])[CH2:25][CH2:26][C:27]([OH:29])=[O:28])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[O:21][CH3:22])=[CH:10][CH:9]=1)C.[OH-].[Na+]>CO>[C:4]([CH2:5][C@H:6]([NH:23][C:24](=[O:30])[CH2:25][CH2:26][C:27]([OH:29])=[O:28])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[O:21][CH3:22])=[CH:10][CH:9]=1)([OH:31])=[O:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59607555HCID 59607555, compound

Product 1

HCID 59607687(R)-4-(1-carboxy-3-(5'-fluoro-2'-methoxybiphenyl-4-yl)propan-2-ylamino)-4-oxobutanoic acidYield 74.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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)

Workup

  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)

Sources & evidence

ORD record
ord-1f16101923364d8a8901b7b95a86cdce
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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