2,5-Dichlorophenol → 4-(2,5-Dichloro-phenoxy)-pyrimidine-5-carboxylic acid ethyl ester

HRID 1025904Notes

Reaction equation

HRID 1025904 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](Cl)=[N:8][CH:9]=[N:10][CH:11]=1)=[O:5])[CH3:2].[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[OH:21].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.F[P-](F)(F)(F)(F)F.[Cu+].C(#N)C.C(#N)C.C(#N)C.C(#N)C>[CH2:1]([O:3][C:4]([C:6]1[C:7]([O:21][C:15]2[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:14]=2[Cl:13])=[N:8][CH:9]=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 662,5-DichlorophenolHCID 10796Cesium carbonateHCID 12684326Ethyl 4-chloropyrimidine-5-carboxylate

Product 1

HCID 673201004-(2,5-Dichloro-phenoxy)-pyrimidine-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 11068737tetrakis(acetonitrile)copper(I) hexafluorophosphateCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 420 mg (2.25 mmol) 4-chloropyrimidine-5-carboxylic acid ethyl ester (commercially available, CAS RN 41103-17-7) and 440 mg (2.7 mmol) 2,5-dichlorophenol (commercially available, CAS RN 583-78-8) in 2.5 mL toluene were added 688 mg (5.17 mmol) cesium carbonate and 168 mg (0.45 mmol) tetrakis(acetonitrile) copper(I) hexafluorophosphate (commercially available, CAS RN 64443-05-6). The reaction was heated to reflux for 2.5 h. The solvent was evaporated and the crude reaction product extracted with ethyl acetate from an aqueous saturated solution of sodium bicarbonate. The organic layer was dried over magnesium sulfate, filtered and evaporated. The resulting product was purified by silica gel chromatography using a MPLC system (silica gel column, CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate yielding 620 mg (88%) of the desired compound as a light yellow viscous oil. MS (ESI): m/z=313.1 [M+H]+.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 2.5 h
  3. customThe solvent was evaporated
  4. customthe crude reaction product
  5. extractionextracted with ethyl acetate from an aqueous saturated solution of sodium bicarbonate
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe resulting product was purified by silica gel chromatography
  10. washeluting with a gradient of n-heptane

Sources & evidence

ORD record
ord-58ab7c6baf114b1ba85ddb0c2160b786
Source dataset
uspto-grants-2014_05
Patent number
US08729091B2

Reaction notes

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