Phosphorus oxychloride → 4-Chloro-2-methylquinoline

HRID 1514812Notes

Reaction equation

HRID 1514812 reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:12])[CH:3]=1.O=P(Cl)(Cl)[Cl:15]>>[Cl:15][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:12])[CH:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1784288112-Methylquinolin-4-ol

Product 1

HCID 779734-Chloro-2-methylquinoline

Conditions

Temperature
80 °C

Procedure

The commercially available 4-hydroxy-2-methylquinoline (6.522 g, 41 mmol) was added portionwise to POCl3 (35 mL) in a round flask at 0° C. with stirring. The homogenous suspension was then immersed into a pre-heated at 80° C. oil bath and continuously refluxed for 4 h. The reaction mixture was cooled to room temperature and the excess POCl3 was distilled out under reduces pressure. The residue was treated carefully with ice (150 g) and then with saturated NaHCO3 aqueous solution (200 mL). The mixture was extracted with CH2Cl2 (100×3 mL), dried over Na2SO4, and evaporated in vacuo to dryness to give known 4-chloro-2-methylquinoline,53 6.10 g (84.14%) as oil, which was pure enough for using in next step. 1H NMR (DMSO) δ 2.61 (3H, s, Me), 7.66 (1H, s, ArH), 7.67-7.71 (1H, m, ArH), 7.82-7.85 (1H, s, ArH), 8.01 (1H, d, J=6.7 Hz, ArH), 8.12-8.14 (1H, s, ArH). Anal. Calcd. for (C10H8ClN): C, 67.62; H, 4.54; N, 7.89. Found: C, 67.62; H, 4.54; N, 7.89.

Workup

  1. temperaturecontinuously refluxed for 4 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. distillationthe excess POCl3 was distilled out
  4. additionThe residue was treated carefully with ice (150 g)
  5. extractionThe mixture was extracted with CH2Cl2 (100×3 mL)
  6. dry with materialdried over Na2SO4
  7. customevaporated in vacuo to dryness
  8. customto give

Sources & evidence

ORD record
ord-be9f53b28c624d31b66545329110c41a
Source dataset
uspto-grants-2012_07
Patent number
US08222297B2

Reaction notes

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