Potassium Carbonate → 2-Chloro-3-fluoro-5-(2,2,3,3-tetrafluoropropoxy)pyridine

HRID 571750Notes

Reaction equation

HRID 571750 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S(O[CH2:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])(=O)=O>CN(C=O)C.C([O-])(O)=O.[Na+].C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([O:8][CH2:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])=[CH:6][N:7]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 37924752,2,3,3-Tetrafluoropropyl trifluoromethanesulfonateHCID 404247372-Chloro-3-fluoro-5-hydroxypyridine

Product 1

HCID 1177387522-Chloro-3-fluoro-5-(2,2,3,3-tetrafluoropropoxy)pyridineYield 83%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

6-Chloro-5-fluoro-pyridin-3-ol (300 mg, 2.03 mmol) is dissolved in DMF (10 mL). Potassium carbonate (562 mg, 4.07 mmol) is added followed by 2,2,3,3-tetrafluoropropyl trifluoromethanesulfonate (591 mg, 2.24 mmol) (For preparation of this reagent, see US2013/143900, Ex 1). The reaction is stirred at room temperature for 18 hours then allowed to stand at room temperature for 4 days. The reaction is diluted with aqueous NaHCO3 and ethyl acetate. The layers are separated and the aqueous layer is extracted with ethyl acetate (2×). The combined organic layers are washed with brine and concentrated. The crude material is purified via silica gel chromatography using a 0-10% ethyl acetate/hexanes gradient to give the title compound (440 mg, 83%). ES/MS (m/e): 262.0 (M+1).

Workup

  1. customFor preparation of this reagent
  2. waitto stand at room temperature for 4 days
  3. customThe layers are separated
  4. extractionthe aqueous layer is extracted with ethyl acetate (2×)
  5. washThe combined organic layers are washed with brine
  6. concentrationconcentrated
  7. customThe crude material is purified via silica gel chromatography

Sources & evidence

ORD record
ord-9c051a0076a041a5b2803ee85616bb22
Source dataset
uspto-grants-2015_05
Patent number
US09029367B2

Reaction notes

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