Oxazole → Dimethyl 5-(oxazol-2-yl)isophthalate

HRID 2071132Notes

Reaction equation

HRID 2071132 reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Li]CCCC.I[C:12]1[CH:13]=[C:14]([C:22]([O:24][CH3:25])=[O:23])[CH:15]=[C:16]([CH:21]=1)[C:17]([O:19][CH3:20])=[O:18]>C1COCC1.CCOC(C)=O.O.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:12]1[CH:21]=[C:16]([C:17]([O:19][CH3:20])=[O:18])[CH:15]=[C:14]([CH:13]=1)[C:22]([O:24][CH3:25])=[O:23]

Participants

9

Reactant 3

HCID 9255OxazoleHCID 2758568Dimethyl 5-iodoisophthalateHCID 178418339Butyllithium

Product 1

HCID 11379968Dimethyl 5-(oxazol-2-yl)isophthalateYield 54%

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of oxazole ((0.28 mL, 4.2 mmol) in THF (10 mL) at −78° C. was added nBuLi (2.8 mL 1.6 N solution in hexane, 4.4 mmol). ZnCl2 (20 mL 0.5M soln, 10 mmol) was added after 30 min and the reaction mixture was warmed up to 0° C. for 1 h. To the resulting mixture was added dimethyl 5-iodoisophthalate (1.28 g, 4.0 mmol) and Pd(PPh3)4 and was heated at reflux for 5 h. The reaction mixture was cooled to room temperature and diluted with EtOAc and H2O. The layers were separated and the organic layer was washed with, brine, dried with Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (20% EtOAc in hexanes) to provide dimethyl 5-(oxazol-2-yl)isophthalate (568 mg, 54%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 5 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customThe layers were separated
  5. washthe organic layer was washed with, brine
  6. dry with materialdried with Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography (20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c0a42131807d4676b485b615686e5698
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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