Oxalyl chloride → 3-Fluoro-4-(5-phenoxybenzo[d]oxazol-2-yl)benzaldehyde

HRID 2075261Notes

Reaction equation

HRID 2075261 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([CH:11]=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[CH:25]=[C:24]([O:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:23]=[CH:22][C:21]=1O.CCN(C(C)C)C(C)C.O.CC1C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl.CN(C)C=O.Cl.O.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:10]=[C:9]([CH:8]=[CH:7][C:3]=1[C:4]1[O:6][C:21]2[CH:22]=[CH:23][C:24]([O:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:25][C:20]=2[N:19]=1)[CH:11]=[O:12]

Participants

11

Reactant 5

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 521998p-Toluenesulfonic acid monohydrateHCID 106795632-Amino-4-phenoxyphenolHCID 184419582-Fluoro-4-formylbenzoic acid

Product 1

HCID 584153063-Fluoro-4-(5-phenoxybenzo[d]oxazol-2-yl)benzaldehyde

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a slurry of 2-fluoro-4-formylbenzoic acid (0.500 g, 3.0 mmol) in 8 mL DCM was added 2 drops N,N-dimethylformamide (0.011 g, 0.15 mmol), followed by oxalyl dichloride (0.39 mL, 4.5 mmol). After 30 min, the reaction became clear, light yellow, and homogeneous. The reaction was evaporated and dried in vacuo. The resulting solid was suspended in 10 mL THF, and 2-amino-4-phenoxyphenol (0.60 g, 3.0 mmol) was added as a solid followed by Hunig's base (0.67 mL, 3.9 mmol). The resulting brown solution became warm, and was allowed to stir for overnight. The reaction was diluted with DCM and 1N HCl. The aq. layer was extracted 1×DCM, and the organics were dried over sodium sulfate, filtered, and concentrated to give a brown solid. This was treated with 4-methylbenzenesulfonic acid hydrate (0.85 g, 4.5 mmol) and 10 mL toluene. The reaction was fitted with a water-cooled reflux condensor and drying tube, and placed in a 120° C. bath for ˜4 h, cooled and partitioned between DCM and 1N NaOH with stirring. The reaction was filtered, and the aq. layer was extracted 1×DCM. The combined organics were dried over sodium sulfate, filtered, and concentrated to give an orange oil which was purified by ISCO, 0-30% EtOAc/hexanes to give title compound as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.10 (s, 1H), 8.45 (t, J=7.5 Hz, 1H), 7.94-8.02 (m, 2H), 7.90 (d, J=9.0 Hz, 1H), 7.54 (d, J=2.0 Hz, 1H), 7.37-7.46 (m, 2H), 7.22 (dd, J=8.8, 2.3 Hz, 1H), 7.15 (t, J=7.3 Hz, 1H), 7.04 (d, J=8.5 Hz, 2H).

Workup

  1. customThe reaction was evaporated
  2. customdried in vacuo
  3. temperatureThe resulting brown solution became warm
  4. extractionThe aq. layer was extracted 1×DCM
  5. dry with materialthe organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a brown solid
  9. temperaturecooled
  10. temperaturereflux condensor
  11. customdrying tube
  12. customplaced in a 120° C.
  13. customfor ˜4 h
  14. temperaturecooled
  15. custompartitioned between DCM and 1N NaOH
  16. stirringwith stirring
  17. filtrationThe reaction was filtered
  18. extractionthe aq. layer was extracted 1×DCM
  19. dry with materialThe combined organics were dried over sodium sulfate
  20. filtrationfiltered
  21. concentrationconcentrated
  22. customto give an orange oil which
  23. customwas purified by ISCO, 0-30% EtOAc/hexanes

Sources & evidence

ORD record
ord-9d138ac2df444343a3c0b1bc2f63fffa
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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