Acetic Anhydride → 2-Hydroxy-4-(4-trifluoromethylphenyl)pyridine

HRID 2390433Notes

Reaction equation

HRID 2390433 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][N+:12]([O-])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.CC(OC(C)=O)=[O:20]>>[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][NH:12][C:11](=[O:20])[CH:10]=2)=[CH:5][CH:4]=1

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 573508294-(4-(Trifluoromethyl)phenyl)pyridine 1-oxide

Product 1

HCID 497584672-Hydroxy-4-(4-trifluoromethylphenyl)pyridineYield 72%

Procedure

A stirred solution of 4-(4-(trifluoromethyl)phenyl)pyridine 1-oxide (465 mg, 1.94 mmol) in Ac2O (10 mL) under nitrogen atmosphere was heated from 110 to 130° C. over 4.5 h. Then the mixture was heated at reflux for 2 h and then allowed to cool. The mixture was concentrated to dryness and then treated with MeOH and water (10 mL, 1:1). After stirring at room temperature for 6 h, the mixture was heated to reflux for 2.5 h. The mixture was allowed to cool and was concentrated to dryness. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 95:5) gave the title compound (336 mg, 72%) as a light brown powder: 1H NMR (500 MHz, CDCl3) δ 12.67 (br s, 1H), 7.76 (d, J=8.2 Hz, 2H), 7.69 (d, J=8.3 Hz, 2H), 7.47 (d, J=6.8 Hz, 1H), 6.80 (d, J=1.6 Hz, 1H), 6.54 (dd, J=6.8, 1.8 Hz, 1H); ESI MS m/z 240 [M+H]+.

Workup

  1. temperatureThen the mixture was heated
  2. temperatureat reflux for 2 h
  3. temperatureto cool
  4. concentrationThe mixture was concentrated to dryness
  5. additiontreated with MeOH and water (10 mL, 1:1)
  6. temperaturethe mixture was heated
  7. temperatureto reflux for 2.5 h
  8. temperatureto cool
  9. concentrationwas concentrated to dryness
  10. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 95:5)

Sources & evidence

ORD record
ord-26b6510c81344f5d982d13dcd4586bf6
Source dataset
uspto-grants-2012_09
Patent number
US08273770B2

Reaction notes

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