Hydrochloric Acid → HCID 24801045, compound

HRID 386453Notes

Reaction equation

HRID 386453 reaction equation
[O:1]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([C:19]2[O:20][C:21]([C:24]3[N:29]=[CH:28][C:27]([C:30]([O:32]C)=[O:31])=[CH:26][CH:25]=3)=[CH:22][N:23]=2)=[O:18])=[CH:11][CH:10]=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]([CH2:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][C:17]([C:19]2[O:20][C:21]([C:24]3[N:29]=[CH:28][C:27]([C:30]([OH:32])=[O:31])=[CH:26][CH:25]=3)=[CH:22][N:23]=2)=[O:18])=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 24800519HCID 24800519, compound

Product 1

HCID 24801045HCID 24801045, compoundYield 81.7%

Reagents, catalysts & solvents 2

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

Procedure

Methyl 6-(2-(3-(4-(phenoxymethyl)phenyl)propanoyl)oxazol-5-yl)pyridine-3-carboxylate (46 mg, 0.10 mmol) was dissolved in THF/H2O (3:2, 10 mL) and LiOH (7 mg, 0.3 mmol) was added. The reaction solution was stirred at room temperature under an atmosphere of Ar for 15 min 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 tritration in ether to provide 6-(2-(3-(4-(phenoxymethyl)phenyl)propanoyl)oxazol-5-yl)pyridine-3-carboxylic acid as a white solid (35 mg, 79%): 1H NMR (THF-d8, 600 MHz) δ 9.18 (d, 1H, J=1.3 Hz), 8.41 (dd, 1H, J=8.2, 2.0 Hz), 7.97 (s, 1H), 7.94 (d, 1H, J=8.2 Hz), 7.35 (d, 2H, J=7.9 Hz), 7.28 (d, 2H, J=7.8 Hz), 7.22 (t, 2H, J=8.0 Hz), 6.95 (d, 2H, J=8.1 Hz), 6.87 (t, 1H, J=7.3 Hz), 2.09 (s, 2H), 3.43 (t, 2H, J=7.6 Hz), 3.06 (t, 2H, J=7.6 Hz); 13C NMR (THF-d8, 150 MHz) δ 187.1, 166.1, 160.1, 158.9, 153.5, 152.2, 150.3, 141.5, 139.2, 136.4, 130.0, 129.3, 129.1, 128.4, 127.5, 121.3, 120.1, 115.5, 70.2, 41.4, 30.1; HR ESI-TOF m/z 429.1443 (M+H+, C25H20N2O5, requires 429.1445).

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 tritration in ether

Sources & evidence

ORD record
ord-3773323de1a8480e9af69eb53e907b1a
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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