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

HRID 2277422Notes

Reaction equation

HRID 2277422 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](O)=[C:9]([C:18]#[N:19])[C:8]2=[O:20])=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:25]>O>[Cl:25][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:7]([CH2:6][C:5]2[CH:21]=[CH:22][C:2]([F:1])=[CH:3][CH:4]=2)[C:8](=[O:20])[C:9]=1[C:18]#[N:19]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 58799228HCID 58799228, compound

Product 1

HCID 210819574-Chloro-1-(4-fluorobenzyl)-2-oxo-1,2-dihydro-quinoline-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To 1-(4-Fluoro-benzyl)-4-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carbonitrile (1 eq, 0.250 g, 0.85 mmole) was added POCl3 neat. The resulting solution was heated to 100° C. for 8 hours, Reaction mixture was added dropwise to water (20 mL) which had been heated to 80° C. then cooled to RT and extracted with ethyl acetate (25 mL×3). Combined organic phase was washed consecutively with water, brine before drying over sodium sulfate. Organic phase was evaporated and the residue was purified by flash chromatography to afford 4-Chloro-1-(4-fluoro-benzyl)-2-oxo-1,2-dihydro-quinoline-3-carbonitrile as a yellow solid (0.156 g, 59%. LCMS calc M+H 313, obs M+H 313).

Workup

  1. customReaction mixture
  2. temperaturehad been heated to 80° C.
  3. temperaturethen cooled to RT
  4. extractionextracted with ethyl acetate (25 mL×3)
  5. washCombined organic phase was washed consecutively with water, brine
  6. dry with materialbefore drying over sodium sulfate
  7. customOrganic phase was evaporated
  8. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-943921b768084df9935e463712609eac
Source dataset
uspto-grants-2015_09
Patent number
US09133164B2

Reaction notes

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