4-Aminophenol → 1-(4-(3-(4-Aminophenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone

HRID 473701Notes

Reaction equation

HRID 473701 reaction equation
F[C:2]1[C:3]([CH:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:16])[CH3:15])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN1CCCC1=O>CCOC(C)=O>[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][C:2]2[C:3]([CH:8]3[CH2:13][CH2:12][N:11]([C:14](=[O:16])[CH3:15])[CH2:10][CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 4034-AminophenolHCID 10796Cesium carbonateHCID 13387N-methyl-2-pyrrolidoneHCID 59351287HCID 59351287, compound

Product 1

HCID 593741621-(4-(3-(4-Aminophenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

1-(4-(3-fluoropyrazin-2-yl)piperidin-1-yl)ethanone (0.153 g, 0.685 mmol), 4-aminophenol (0.079 g, 0.720 mmol), cesium carbonate (0.246 g, 0.754 mmol), and 1-methyl-2-pyrrolidinone (0.685 mL, 0.685 mmol) were combined in a sealed tube and heated at 80° C. for 20 h. The cooled reaction mixture was diluted with EtOAc and washed with water; the aqueous layer was back-extracted with EtOAc (1×). The organic layers were combined, dried (MgSO4), filtered, and concentrated in vacuo. ISCO purification (20% to 80% EtOAc/Hexanes) afforded 1-(4-(3-(4-aminophenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone as a light brown oil. MS (ESI, pos. ion) m/z: 313.0 (M+1).

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water
  3. extractionthe aqueous layer was back-extracted with EtOAc (1×)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customISCO purification (20% to 80% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-309c1eeab3ee4f1b8e3e89c29bc0b0db
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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