Acetic Anhydride → 4-(4-Chlorophenyl)-2-hydroxypyridine

HRID 1020537Notes

Reaction equation

HRID 1020537 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N+:11]([O-])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C(OC(=O)C)(=[O:17])C>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][NH:11][C:10](=[O:17])[CH:9]=2)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 686579264-(4-Chlorophenyl)pyridine 1-oxide

Product 1

HCID 189872944-(4-Chlorophenyl)-2-hydroxypyridineYield 48%

Procedure

4-(4-Chlorophenyl)pyridine 1-oxide (1.04 g, 5.07 mmol) and acetic anhydride (25 mL) were heated to reflux for 24 h. The mixture was then concentrated, and 1 N NaOH (10 mL) in MeOH (10 mL) was added. The reaction mixture was heated to reflux for 1 h, then cooled, concentrated, and purified by flash column chromatography (silica gel, methylene chloride/MeOH 100:0 to 98:2 to 95:5 then 90:10) providing the title compound (500 mg, 48%) as an off-white solid: 1H NMR (300 MHz, CDCl3) δ 11.64 (s, 1H), 7.73 (d, J=8.6 Hz, 2H), 7.54 (d, J=8.6 Hz, 2H), 7.46 (d, J=6.8 Hz, 1H), 6.60 (d, J=1.4 Hz, 1H), 6.50 (dd, J=6.9, 1.8 Hz, 1H).

Workup

  1. temperatureto reflux for 24 h
  2. concentrationThe mixture was then concentrated
  3. addition1 N NaOH (10 mL) in MeOH (10 mL) was added
  4. temperatureThe reaction mixture was heated
  5. temperatureto reflux for 1 h
  6. temperaturecooled
  7. concentrationconcentrated
  8. custompurified by flash column chromatography (silica gel, methylene chloride/MeOH 100:0 to 98:2 to 95:5

Sources & evidence

ORD record
ord-73cb5594bd6f4eeeb110f3fd4c995277
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

Loading…