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

HRID 970507Notes

Reaction equation

HRID 970507 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-e9edc79c4bf64d9fa74d933f34b65524
Source dataset
uspto-grants-2007_12
Patent number
US07312220B2

Reaction notes

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