Hydrochloric Acid → HCID 24800865, compound

HRID 386449Notes

Reaction equation

HRID 386449 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]=[CH:27][C:26]([C:29]([O:31]C)=[O:30])=[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]=[CH:27][C:26]([C:29]([OH:31])=[O:30])=[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 24800000HCID 24800000, compound

Product 1

HCID 24800865HCID 24800865, compoundYield 57.5%

Reagents, catalysts & solvents 2

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

Procedure

Methyl 6-(2-(3-(4-phenoxyphenyl)propanoyl)oxazol-5-yl)pyridine-3-carboxylate (57 mg, 0.13 mmol) was dissolved in THF/H2O (3:2, 7.5 mL) and LiOH (10 mg, 0.40 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-3-carboxylic acid as a light tan solid (31 mg, 56%): 1H NMR (THF-d8, 600 MHz) δ 9.18 (s, 1H), 8.41 (dd, 1H, J=8.4, 1.8 Hz), 7.98 (s, 1H), 7.97 (d, 1H, J=8.4 Hz), 7.30-7.25 (m, 4H), 7.03 (t, 1H, J=7.8 Hz), 6.94 (d, 2H, J=7.8 Hz), 6.91 (d, 2H, J=8.4 Hz), 3.42 (t, 2H, J=7.8 Hz), 3.04 (t, 2H, J=7.8 Hz); 13C NMR (CDCl3, 150 MHz) δ 187.3, 166.2, 159.7, 158.9, 156.7, 153.7, 152.4, 150.5, 139.4, 137.1, 130.7, 130.6, 129.3, 127.6, 123.8, 120.3, 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-1ad1d6e2accf4d319cf1737e5b95e979
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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