Phosphorus oxychloride → (6-Bromo-4-chloroquinolin-3-yl)(cyclopropyl)methanone

HRID 2271512Notes

Reaction equation

HRID 2271512 reaction equation
P(Cl)(Cl)([Cl:3])=O.[Br:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[CH:12][C:11]([C:17]([CH:19]1[CH2:21][CH2:20]1)=[O:18])=[C:10]2O>>[Br:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[CH:12][C:11]([C:17]([CH:19]1[CH2:21][CH2:20]1)=[O:18])=[C:10]2[Cl:3]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178519797HCID 178519797, compound

Product 1

HCID 66715111(6-Bromo-4-chloroquinolin-3-yl)(cyclopropyl)methanoneYield 27.6%

Conditions

Temperature
0 °C

Procedure

Phosphoryl chloride (50 mL, 0.547 mol) was cooled to 0° C. and (6-bromo-4-hydroxyquinolin-3-yl)(cyclopropyl)methanone (21 g, 67.7 mmol) was added. The reaction mixture was stirred at 0° C. for 2 h, at room temperature for 2 h and concentrated. The residue was dissolved in methylene chloride and poured into cold 30% aq. ammonium hydroxide. The aqueous layer was separated and extracted with methylene chloride. The combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by a silica plug to afford the desired product (5.8 g, 22%) as a brown solid: 1H NMR (300 MHz, CDCl3) δ 8.91 (s, J=6.4 Hz, 1H), 8.55-8.49 (m, 1H), 8.07-7.97 (m, 1H), 7.91 (dd, J=8.9, 2.1 Hz, 1H), 2.69-2.54 (m, 1H), 1.50-1.40 (m, 2H), 1.28-1.19 (m, 2H).

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in methylene chloride
  3. additionpoured into cold 30% aq. ammonium hydroxide
  4. customThe aqueous layer was separated
  5. extractionextracted with methylene chloride
  6. dry with materialThe combined organics were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by a silica plug

Sources & evidence

ORD record
ord-795ade0cf6f14a18aec42991738c3951
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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