Hydrochloric Acid → HCID 24799998, compound

HRID 386448Notes

Reaction equation

HRID 386448 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]([C:18]2[O:19][C:20]([C:23]3[N:28]=[C:27]([C:29]([O:31]C)=[O:30])[CH:26]=[CH:25][CH:24]=3)=[CH:21][N:22]=2)=[O:17])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-].Cl>C1COCC1.O.CCOC(C)=O>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([CH2:14][CH2:15][C:16]([C:18]2[O:19][C:20]([C:23]3[N:28]=[C:27]([C:29]([OH:31])=[O:30])[CH:26]=[CH:25][CH:24]=3)=[CH:21][N:22]=2)=[O:17])=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 24800864HCID 24800864, compound

Product 1

HCID 24799998HCID 24799998, compoundYield 91.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

Methyl 6-(2-(3-(4-phenoxyphenyl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate (356 mg, 0.831 mmol) was dissolved in THF/H2O (3:2, 75 mL) and LiOH (59 mg, 2.5 mmol) was added. The reaction solution was stirred at room temperature under an atmosphere of Ar for 2 h before the addition of 1 N HCl to adjust the solution to an acidic pH to quench the reaction. The reaction solution was diluted with EtOAc and the organic and aqueous layers were separated. The aqueous layer was extracted with EtOAc (3×). The organic phases were combined and washed with saturated aqueous NaCl, dried over Na2SO4, and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 1% AcOH/EtOAc) to provide 6-(2-(3-(4-phenoxyphenyl)propanoyl)oxazol-5-yl)pyridine-2-carboxylic acid as a light yellow solid (314 mg, 91%): 1H NMR (THF-d8, 500 MHz) δ 8.11-8.03 (m, 4H), 7.30-7.25 (m, 4H), 7.03 (t, 1H, J=8.0 Hz), 6.94 (d, 2H, J=8 Hz), 6.91 (d, 2H, J=8.5 Hz), 3.43 (t, 2H, J=7.5 Hz), 3.04 (t, 2H, J=7.5 Hz); 13C NMR (THF-d8, 500 MHz) δ 187.3, 165.7, 158.9, 156.7, 153.6, 150.1, 147.2, 139.7, 137.1, 130.7, 130.6, 128.7, 125.5, 123.8, 123.7, 120.0, 119.4, 41.7, 29.8; HR ESI-TOF m/z 415.1284 (M+H+, C24H18N2O5, requires 415.1288).

Workup

  1. customto quench
  2. customthe reaction
  3. customthe organic and aqueous layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc (3×)
  5. washwashed with saturated aqueous NaCl
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography (SiO2, 1% AcOH/EtOAc)

Sources & evidence

ORD record
ord-3e431813a748483c9b066d7c8577a531
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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