4-(3-Chloropyrazin-2-yloxy)benzenamine → 4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)aniline

HRID 555865Notes

Reaction equation

HRID 555865 reaction equation
Cl[C:2]1[C:3]([O:8][C:9]2[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[O:16]1[CH2:21][CH2:20][CH:19]([Mg]Cl)[CH2:18][CH2:17]1>C1COCC1.CN1C(=O)CCC1.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Fe+3]>[O:16]1[CH2:21][CH2:20][CH:19]([C:2]2[C:3]([O:8][C:9]3[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH2:18][CH2:17]1

Participants

6

Reactant 2

HCID 201339744-(3-Chloropyrazin-2-yloxy)benzenamineHCID 178478991HCID 178478991, compound

Product 1

HCID 593511704-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)aniline

Reagents, catalysts & solvents 3

HCID 5483663Ferric acetylacetonateCatalystHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a round bottomed flask was added 4-(3-chloropyrazin-2-yloxy)aniline (1.2276 g, 5.54 mmol) dissolved in a mixture of THF (8.86 mL) and NMP (2.215 mL). Iron(iii) acetylacetonate (0.098 g, 0.277 mmol) was added and the temperature was brought to 0° C. (Tetrahydro-2H-pyran-4-yl)magnesium chloride (8.31 mL, 6.65 mmol) was added dropwise to the reaction mixture. Upon completion, the reaction was quenched with saturated ammonia chloride solution. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with water, brine, dried with magnesium sulfate, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (120 g), eluting with a gradient of 10% to 100% EtOAc in hexane, to provide 4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)aniline.

Workup

  1. customwas brought to 0° C.
  2. additionwas added dropwise to the reaction mixture
  3. customUpon completion, the reaction was quenched with saturated ammonia chloride solution
  4. additionThe reaction mixture was diluted with water
  5. extractionextracted with EtOAc
  6. extractionThe organic extract
  7. washwas washed with water, brine
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customchromatographed through a Redi-Sep® pre-packed silica gel column (120 g)
  12. washeluting with a gradient of 10% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-5bc629477eb44c58948f82c9c74f744a
Source dataset
uspto-grants-2011_11
Patent number
US08053438B2

Reaction notes

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