Phosphorus oxychloride → 4-Chloro-6-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

HRID 346613Notes

Reaction equation

HRID 346613 reaction equation
C1([NH:7][C:8]([C:10]2[C:11](=[O:23])[N:12]([CH3:22])[C:13]3[C:18]([C:19]=2O)=[CH:17][C:16]([F:21])=[CH:15][CH:14]=3)=O)CCCCC1.P(Cl)(Cl)([Cl:26])=O>>[Cl:26][C:19]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:21])[CH:17]=2)[N:12]([CH3:22])[C:11](=[O:23])[C:10]=1[C:8]#[N:7]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 694755656-Fluoro 4-hydroxy-1-methyl-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid cyclohexylamide

Product 1

HCID 210819614-Chloro-6-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrileYield 56%

Procedure

A solution of Compound 44 (2 g, 6.28 mmol) in 20 ml neat phosphorus oxychloride was heated at 90° C. for 5 h. The solvent was evaporated under reduced pressure. The residue was suspended in ice water and neutralized by solid sodium bicarbonate. The solids formed were filtered, washed by water, and purified by flash chromatography eluting with 1% methanol in dichloromethane to yield 0.80 g (56%) of yellow solids. M.P. 258° C. 1H NMR (DMSO-d6): δ 3.67 (s, 3H), 7.78–7.89 (m, 3H). EIMS m/z 259 (M+23).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customThe solids formed
  3. filtrationwere filtered
  4. washwashed by water
  5. custompurified by flash chromatography
  6. washeluting with 1% methanol in dichloromethane

Sources & evidence

ORD record
ord-dce2d0c6cb8c4abea344fac7f0c4ded5
Source dataset
uspto-grants-2007_02
Patent number
US07173036B2

Reaction notes

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