Sodium Hydroxide → HCID 135973207, compound

HRID 1469630Notes

Reaction equation

HRID 1469630 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@@H:15]([NH:24][C:25]([C:27]3[NH:31][C:30](=[O:32])[O:29][N:28]=3)=[O:26])[CH2:16][C@@H:17]([CH3:23])[C:18]([O:20]CC)=[O:19])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][C@@H:15]([NH:24][C:25]([C:27]3[NH:31][C:30](=[O:32])[O:29][N:28]=3)=[O:26])[CH2:16][C@@H:17]([CH3:23])[C:18]([OH:20])=[O:19])=[CH:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 135973210HCID 135973210, compound

Product 1

HCID 135973207HCID 135973207, compoundYield 93.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (2R,4S)-ethyl 5-(3′-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3-carboxamido)pentanoate (25 mg, 0.055 mmol) in MeOH (2 mL) is added aqueous 1 N NaOH (4 mL). After stirring at room temperature for 2 hours, the crude is quenched with 1N HCl and concentrated under reduced pressure to remove MeOH. The crude 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 (2R,4S)-5-(3′-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3-carboxamido)pentanoic acid (22 mg). HPLC retention time=1.64 minutes (condition B); MS (m+1)=430.2; 1H NMR (400 MHz, CD3OD) δ ppm 1.18 (d, J=7.1 Hz, 3 H) 1.68 (ddd, J=14.3, 10.5, 4.0 Hz, 1 H) 1.99-2.05 (m, 1 H) 2.55 (ddd, J=10.2, 6.8, 3.9 Hz, 1 H) 2.80-2.97 (m, 2 H) 4.27-4.44 (m, 1 H) 7.28-7.35 (m, 3 H) 7.39 (t, J=7.8 Hz, 1 H) 7.49-7.55 (m, 3 H) 7.58 (t, J=1.9 Hz, 1 H)

Workup

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

Sources & evidence

ORD record
ord-1c8d0635bf9545af827a94db5e0c57cd
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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