Phosphorus oxychloride → 4-Chloro-1-(4-fluorobenzyl)-6-methyl-2-oxo-1,2-dihydro-quinoline-3-carbonitrile

HRID 346594Notes

Reaction equation

HRID 346594 reaction equation
C1([NH:7][C:8]([C:10]2[C:11](=[O:30])[N:12]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[C:13]3[C:18]([C:19]=2O)=[CH:17][C:16]([CH3:21])=[CH:15][CH:14]=3)=O)CCCCC1.P(Cl)(Cl)([Cl:33])=O>>[Cl:33][C:19]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH3:21])[CH:17]=2)[N:12]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[C:11](=[O:30])[C:10]=1[C:8]#[N:7]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 694790651-(4-Fluorobenzyl)-4-hydroxy-6-methyl-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid cyclohexylamide

Product 1

HCID 210819584-Chloro-1-(4-fluorobenzyl)-6-methyl-2-oxo-1,2-dihydro-quinoline-3-carbonitrileYield 47%

Procedure

A solution of Compound 19 (5 g, 12.24 mmol) in 30 mL neat phosphorus oxychloride was heated at 100° C. for 3 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 1.90 g (47%) of yellow solids. M.P. 206° C. 1H NMR (DMSO-d6): δ 2.40 (s, 3H), 5.52 (s, 2H), 7.12–7.15 (m, 2H), 7.30–7.33 (m, 2H), 7.46 (d, J=8.7 Hz, 1H), 7.64 (dd, J=1.2, 8.7 Hz, 1H), 7.89 (d, J=1.2 Hz, 1H). EIMS m/z 327 (M+1).

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-db77042fcc854d30b79c494738182748
Source dataset
uspto-grants-2007_02
Patent number
US07173036B2

Reaction notes

Loading…