Ethyl Acetate → (6-Bromo-4-chloro-7-fluoroquinolin-3-yl)(cyclopropyl)methanone

HRID 2271524Notes

Reaction equation

HRID 2271524 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][C:6]([C:13]([CH:15]1[CH2:17][CH2:16]1)=[O:14])=[C:5]2O.[OH-].[NH4+].C(OCC)(=O)C.P(Cl)(Cl)([Cl:29])=O>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][C:6]([C:13]([CH:15]1[CH2:17][CH2:16]1)=[O:14])=[C:5]2[Cl:29]

Participants

5

Reactant 4

HCID 8857Ethyl AcetateHCID 14923Ammonium HydroxideHCID 24813Phosphorus oxychlorideHCID 178519813HCID 178519813, compound

Product 1

HCID 66715407(6-Bromo-4-chloro-7-fluoroquinolin-3-yl)(cyclopropyl)methanoneYield 42%

Procedure

(6-Bromo-7-fluoro-4-hydroxyquinolin-3-yl)(cyclopropyl)methanone (3.35 g, 10.8 mmol) was suspended in phosphoryl chloride (10 mL) at 0° C. The reaction was warmed to room temperature and stirred overnight. After this time 2M ammonium hydroxide was added dropwise until a solid formed. Ethyl acetate was added and the layers were separated. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to afford the desired product (1.5 g, 42%) as an off-white solid: 1H NMR (300 MHz, CDCl3) δ 8.92 (s, 1H), 8.63 (d, J=7.2 Hz, 1H), 7.84 (d, J=8.9 Hz, 1H), 2.70-2.45 (m, 1H), 1.55-1.35 (m, 2H), 1.35-1.05 (m, 2H).

Workup

  1. customformed
  2. customthe layers were separated
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-7e16439930ab460598f2295364edcab9
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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