Sodium Hydroxide → (2R,4S)-5-(3'-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)pentanoic acid

HRID 2384053Notes

Reaction equation

HRID 2384053 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[O:28][C:29](=[O:32])[NH:30][N:31]=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[O:28][C:29](=[O:32])[NH:30][N:31]=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 59608150(2R,4S)-ethyl 5-(3'-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)pentanoate

Product 1

HCID 59608155(2R,4S)-5-(3'-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)pentanoic acidYield 72.8%

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-1,3,4-oxadiazole-2-carboxamido)pentanoate (91 mg, 0.198 mmol) in MeOH (2 mL) is added aqueous 1N NaOH (4 mL, 4 mmol). After stirring at room temperature for 2 hours, the crude is quenched with 1N HCl and 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 (2R,4S)-5-(3′-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)pentanoic acid (62 mg). HPLC retention time=1.60 minutes (condition B); MS (m+1)=430.1; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.01-1.12 (d, J=7.1 Hz, 3H) 1.60 (ddd, J=13.8, 9.9, 4.3 Hz, 1H) 1.85 (ddd, J=13.6, 9.6, 4.0 Hz, 1H) 2.35-2.47 (m, 1H) 2.79 (dd, J=13.7, 7.8 Hz, 1H) 2.86 (dd, J=13.7, 7.8 Hz, 1H) 4.11-4.28 (m, 1H) 7.28 (d, J=8.3 Hz, 2H) 7.35-7.43 (m, 1H) 7.47 (t, J=7.8 Hz, 1H) 7.57-7.65 (m, 3H) 7.70 (t, J=1.8 Hz, 1H) 8.84 (d, J=8.8 Hz, 1H) 12.05 (br. s., 1H) 12.92 (s, 1H).

Workup

  1. customthe crude is quenched with 1N HCl
  2. concentrationconcentrated under reduced pressure
  3. customto remove MeOH
  4. additionis 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-5ecbc9382c26486e99485feb88b8b7de
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

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