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

HRID 270571

Reaction equation

HRID 270571 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-1166b3494f0f4aeb967b7d823ee371ed
Source dataset
uspto-grants-2008_11
Patent number
US07449467B2

Linked notes

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