Quinoline → 2-Chloro-3-nitro-5-(trifluoromethyl)pyridine

HRID 1044589Notes

Reaction equation

HRID 1044589 reaction equation
P(Cl)(Cl)([Cl:3])=O.N1C2C(=CC=CC=2)C=CC=1.[N+:16]([C:19]1[C:20](O)=[N:21][CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)([O-:18])=[O:17].C([O-])([O-])=O.[Na+].[Na+]>O>[Cl:3][C:20]1[C:19]([N+:16]([O-:18])=[O:17])=[CH:24][C:23]([C:25]([F:28])([F:27])[F:26])=[CH:22][N:21]=1

Participants

6

Reactant 4

HCID 7047QuinolineHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 178526653HCID 178526653, compound

Product 1

HCID 47369502-Chloro-3-nitro-5-(trifluoromethyl)pyridineYield 55%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of phosphoryl chloride (2.0 mL, 21.2 mmol) and quinoline (1.30 mL, 10.8 mmol) was added solid powder 3-nitro-5-(trifluoromethyl)pyridin-2-ol (4.00 g, 18.3 mmol) (95% purity). The resulting dark brown thick suspension was heated to reflux for 4 h and gradually turned into a very cloudy dark brown solution. After cooling to 100° C., water (11 mL) was slowly added to the mixture which was further cooled to room temperature and neutralized carefully with Na2CO3. The resulting solution was extracted with EtOAc three times. The extracts were combined, dried over MgSO4, filtered, and evaporated in vacuo. The residue was purified by flash chromatography on silica gel (EtOAc/hexanes 30:70) to afford 2.28 g of desired product.

Workup

  1. temperatureThe resulting dark brown thick suspension was heated
  2. temperatureto reflux for 4 h
  3. extractionThe resulting solution was extracted with EtOAc three times
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (EtOAc/hexanes 30:70)

Sources & evidence

ORD record
ord-8fd5499a622e44838d7c9681913202a2
Source dataset
uspto-grants-2013_10
Patent number
US08563582B2

Reaction notes

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