Ammonia → HCID 86682953, compound

HRID 1497093Notes

Reaction equation

HRID 1497093 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([CH:17]([CH3:19])[CH3:18])=[N:7][C:8]2[C:13]([C:14]=1O)=[CH:12][C:11]([Cl:16])=[CH:10][CH:9]=2)=[O:4].N.P(Cl)(Cl)([Cl:23])=O>>[CH3:1][O:2][C:3]([C:5]1[C:6]([CH:17]([CH3:19])[CH3:18])=[N:7][C:8]2[C:13]([C:14]=1[Cl:23])=[CH:12][C:11]([Cl:16])=[CH:10][CH:9]=2)=[O:4]

Participants

4

Reactant 3

HCID 222AmmoniaHCID 24813Phosphorus oxychlorideHCID 178497915HCID 178497915, compound

Product 1

HCID 86682953HCID 86682953, compoundYield 61%

Procedure

A mixture of 6-chloro-4-hydroxy-2-isopropyl-quinoline-3-carboxylic acid methyl ester (prepared as described in example 20 step A, 2 g, 7.15 mmol) and phosphorous oxychloride (10 ml) under nitrogen was refluxed for 1 h. After cooling the reaction mixture to room temperature, the mixture was poured onto ice cold water and the pH of the aqueous phase was adjusted to 7 with aqueous ammonia solution. The aqueous phase was extracted with ethyl acetate and the combined organic phases were washed with brine, dried over sodium sulfate and concentrated in vacuo to give a crude residue which was purified by flash column chromatography (100-200 mesh silica, eluting with 5-10% EtOAc in hexane) to afford pure 4,6-dichloro-2-isopropyl-quinoline-3-carboxylic acid methyl ester (1.3 g, 61%) as pale yellow solid. LC-MS: 298 (M+H)+.

Workup

  1. temperaturewas refluxed for 1 h
  2. additionthe mixture was poured onto ice cold water
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. washthe combined organic phases were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a crude residue which
  8. customwas purified by flash column chromatography (100-200 mesh silica, eluting with 5-10% EtOAc in hexane)

Sources & evidence

ORD record
ord-faad1c6f7f884337941363601ffc9bb2
Source dataset
uspto-grants-2015_12
Patent number
US09199938B2

Reaction notes

Loading…