Ethanol → Ethyl 3-chloro-5-(trifluoromethyl)pyridine-2-carboxylate

HRID 650476

Reaction equation

HRID 650476 reaction equation
Cl[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[CH2:13]([OH:15])C.[C]=[O:17].C(N([CH2:23][CH3:24])CC)C>[Cl-].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd+2]>[CH2:23]([O:17][C:13]([C:2]1[C:7]([Cl:8])=[CH:6][C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1)=[O:15])[CH3:24]

Participants

6

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 1122342,3-Dichloro-5-(trifluoromethyl)pyridineHCID 178418416HCID 178418416, compound

Product 1

HCID 22013558Ethyl 3-chloro-5-(trifluoromethyl)pyridine-2-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 84124Bis(triphenylphosphine)palladium chlorideCatalyst

Conditions

Temperature
110 °C

Procedure

An autoclave is charged with 200 g of 2,3-dichloro-5-trifluoromethylpyridine, 1.85 liters of ethanol, 260 ml of triethylamine and 6.5 g of palladium bis(triphenylphosphine) dichloride (PdCl2(PPh3)2). At 25° C. a pressure of 110 bars is then applied with carbon monoxide and the mixture is maintained at 110° C. for 24 hours. After cooling to 25° C., the crude mixture is concentrated to a thick slurry, which is then partitioned between dilute sodium chloride solution and ethyl acetate. After extraction by shaking, and separation of the phases, the ethyl acetate phase is washed with water, dried over sodium sulfate and concentrated to dryness. The crude product is distilled under a high vacuum of 0.035 mbar. 200 g of the desired product are obtained in the form of a yellow oil having a boiling point of 67-70° C./0.035 mbar (yield 85% of the theoretical yield).

Workup

  1. customAt 25° C.
  2. temperatureAfter cooling to 25° C.
  3. concentrationthe crude mixture is concentrated to a thick slurry, which
  4. customis then partitioned between dilute sodium chloride solution and ethyl acetate
  5. extractionAfter extraction
  6. customseparation of the phases
  7. washthe ethyl acetate phase is washed with water
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated to dryness
  10. distillationThe crude product is distilled under a high vacuum of 0.035 mbar

Sources & evidence

ORD record
ord-046dd745272d4d8daefffc6dca8299b2
Source dataset
uspto-grants-2001_08
Patent number
US06274536B1

Linked notes

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