Sodium Chloride → 4-[4-(Trifluoromethoxy)phenoxy]pyridine

HRID 1799511Notes

Reaction equation

HRID 1799511 reaction equation
Cl.Cl[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[F:9][C:10]([F:20])([F:19])[O:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+].[Na+].[Cl-]>C(OCC)(=O)C.O.CN(C=O)C>[F:9][C:10]([F:19])([F:20])[O:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][C:3]2[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=2)=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 11430Potassium CarbonateHCID 70015p-(Trifluoromethoxy)phenolHCID 818524-Chloropyridine hydrochloride

Product 1

HCID 453809774-[4-(Trifluoromethoxy)phenoxy]pyridineYield 52%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
34 °C

Procedure

4-Chloropyridine hydrochloride (17.3 g), 4-Trifluoromethoxyphenol (24.6 g), K2CO3 (35.1 g) and DMF (173 mL) were placed in a vessel and stirred at 28-40° C. for 1.5 hr. and then stirred at 75-84° C. for 6 hr. and then stirred at 139-146° C. for 34.5 hr. The reaction mixture was then cooled to room temperature and water (256 mL), a small amount of NaCl and ethyl acetate (256 mL) were added. The organic material was taken up in ethyl acetate. The organic layer was washed with water (256 mL) and a small amount of NaCl. And then the organic layer was extracted three times with 10 v/v % HCl (256 mL×3). The organic material was taken up in 10 v/v % HCl. And then the aqueous layer was basified to pH 9 by NaOH and was extracted with ethyl acetate (256 mL). The organic material was taken up in ethyl acetate. The organic layer was washed with water (256 mL) and a small amount of NaCl. The organic layer was condensed under reduced pressure to give 15.3 g (52.0% yield) of a brown oily target compound.

Workup

  1. stirringand then stirred at 75-84° C. for 6 hr
  2. stirringand then stirred at 139-146° C. for 34.5 hr
  3. temperatureThe reaction mixture was then cooled to room temperature
  4. washThe organic layer was washed with water (256 mL)
  5. extractionAnd then the organic layer was extracted three times with 10 v/v % HCl (256 mL×3)
  6. extractionwas extracted with ethyl acetate (256 mL)
  7. washThe organic layer was washed with water (256 mL)
  8. customcondensed under reduced pressure

Sources & evidence

ORD record
ord-959741d0451d4b9689145c53388639ff
Source dataset
uspto-grants-2013_01
Patent number
US08344148B2

Reaction notes

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