Sodium Hydroxide → HCID 59608278, compound

HRID 1469636Notes

Reaction equation

HRID 1469636 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:31][C:30]([CH2:32][CH3:33])=[N:29][CH:28]=3)=[O:26])[CH2:16][CH: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:13]=[CH:12][C:11]([CH2:14][C@@H:15]([NH:24][C:25]([C:27]3[O:31][C:30]([CH2:32][CH3:33])=[N:29][CH:28]=3)=[O:26])[CH2:16][C@H:17]([CH3:23])[C:18]([OH:20])=[O:19])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86648211HCID 86648211, compound

Product 1

HCID 59608278HCID 59608278, compoundYield 17.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Next, to a solution of (4S)-ethyl 5-(3′-chlorobiphenyl-4-yl)-4-(2-ethyloxazole-5-carboxamido)-2-methylpentanoate (264 mg, 0.56 mmol) in MeOH (2 mL) is added aqueous 1N NaOH (4 mL) 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 is purified by chiral-HPLC(OJ-H, 15% EtOH(0.1% TFA)/Heptane), and then lyophilized to give (2S,4S)-5-(3′-chlorobiphenyl-4-yl)-4-(2-ethyloxazole-5-carboxamido)-2-methylpentanoic acid (43 mg), HPLC retention time=1.63 minutes (condition B); MS (m+1)=441.2; 1 H NMR (400 MHz, CD3OD) δ ppm 1 H NMR (400 MHz, CD3OD) δ ppm 1.17 (d, J=7.1 Hz, 3 H) 1.35 (t, J=7.7 Hz, 3 H) 1.69 (ddd, J=14.0, 8.3, 3.9 Hz, 1 H) 2.06 (ddd, J=14.1, 10.8, 5.9 Hz, 1 H) 2.39-2.55 (m, 1 H) 2.85 (q, J=7.6 Hz, 2 H) 2.90 (dd, J=13.4, 7.6 Hz, 1 H) 2.95 (dd, J=13.1, 5.8 Hz, 1 H) 4.31-4.52 (m, 1 H) 7.26-7.35 (m, 3 H) 7.38 (t, J=7.8 Hz, 1 H) 7.46-7.55 (m, 4 H) 7.57 (t, J=1.9 Hz, 1 H) and (2R,4S)-5-(3′-chlorobiphenyl-4-yl)-4-(2-ethyloxazole-5-carboxamido)-2-methylpentanoic acid (60 mg). HPLC retention time=1.62 minutes (condition B); MS (m+1)=441.2; 1 H NMR (400 MHz, CD3OD) δ ppm 1.18 (d, J=7.1 Hz, 3 H) 1.35 (t, J=7.6 Hz, 3 H) 1.69 (ddd, J=14.1, 10.4, 4.3 Hz, 1 H) 2.01 (ddd, J=14.0, 10.0, 3.8 Hz, 1 H) 2.46-2.63 (m, 1 H) 2.85 (q, J=7.6 Hz, 2 H) 2.91 (d, J=7.1 Hz, 2 H) 4.30-4.49 (m, 1 H) 7.26-7.34 (m, 3 H) 7.38 (t, J=7.8 Hz, 1 H) 7.46-7.52 (m, 3 H) 7.52 (s, 1 H) 7.56 (t, J=1.9 Hz, 1 H) 8.31 (d, J=9.1 Hz, 1 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)
  9. customis purified by chiral-HPLC(OJ-H, 15% EtOH(0.1% TFA)/Heptane), and

Sources & evidence

ORD record
ord-e73da0e6807946a2a1f7fbf1d265778d
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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