Triethylamine → 2-Fluoro-5-(4-methylbenzoxazol-2-yl)nitrobenzene

HRID 74213Notes

Reaction equation

HRID 74213 reaction equation
[F:1][C:2]1[C:3]([N+:11]([O-:13])=[O:12])=[C:4]([CH:8]=[CH:9][CH:10]=1)C(O)=O.S(Cl)(Cl)=O.[OH:18][C:19]1[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[C:20]=1[NH2:21].[CH2:27](N(CC)CC)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C=O)C.C1(C)C=CC=CC=1.O.O1CCCC1>[F:1][C:2]1[CH:10]=[CH:9][C:8]([C:27]2[O:18][C:19]3[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[C:20]=3[N:21]=2)=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 30141382-Amino-m-cresolHCID 189159203-Fluoro-2-nitrobenzoic acid

Product 1

HCID 674986872-Fluoro-5-(4-methylbenzoxazol-2-yl)nitrobenzeneYield 37%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3-fluoro-2-nitrobenzoic acid (1.00 g, 5.40 mmol) and DMF (1 drop) in toluene (10 mL) was added thionyl chloride (0.78 g, 6.56 mmol) and this was stirred at reflux for 3 hours. After the reaction was complete, concentration at reduced pressure gave a residue that was added to 2-hydroxy-6-methylaniline (0.66 g, 5.4 mmol), triethylamine (0.66 g, 6.5 mmol) and tetrahydrofuran (5 mL), and this was stirred at room temperature for 3 hours. After the reaction was complete, water (50 mL) was added, and this was extracted with ethyl acetate. After the organic layer was dried over anhydrous sodium sulfate, filtration and concentration gave crystals that were added to toluene (20 mL), to which p-toluenesulfonic acid hydrate (1.14 g, 5.99 mmol) was next added and this was stirred at reflux for 2 hours. After concentration of the solvent at reduced pressure, water (5 mL) was added, after which this was extracted with ethyl acetate. The organic layer obtained was dried over anhydrous sodium sulfate, after which it was filtered and concentrated to yield the title compound (0.50 g, 37% yield) as a light brown solid.

Workup

  1. temperatureat reflux for 3 hours
  2. concentrationconcentration at reduced pressure
  3. customgave a residue that
  4. stirringthis was stirred at room temperature for 3 hours
  5. extractionthis was extracted with ethyl acetate
  6. dry with materialAfter the organic layer was dried over anhydrous sodium sulfate, filtration and concentration
  7. customgave crystals that
  8. additionwas next added
  9. stirringthis was stirred
  10. temperatureat reflux for 2 hours
  11. extractionafter which this was extracted with ethyl acetate
  12. customThe organic layer obtained
  13. dry with materialwas dried over anhydrous sodium sulfate
  14. filtrationafter which it was filtered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-139176261c2c4472bb24c540702aa958
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Reaction notes

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