4-Aminophenol → 4-(6-Fluoropyrimidin-4-yloxy)benzenamine

HRID 1993545Notes

Reaction equation

HRID 1993545 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].[H][H].[F:13][C:14]1[CH:19]=[C:18](F)[N:17]=[CH:16][N:15]=1>O1CCOCC1>[F:13][C:14]1[N:15]=[CH:16][N:17]=[C:18]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[CH:19]=1

Participants

6

Reactant 4

HCID 4034-AminophenolHCID 24758Sodium hydrideHCID 1377174,6-DifluoropyrimidineHCID 178418361HCID 178418361, compound

Product 1

HCID 586594294-(6-Fluoropyrimidin-4-yloxy)benzenamine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

4-Amino-phenol (0.135 g, 1.21 mmol) is added in one portion to a suspension of NaH (60% free-flowing powder moistened with oil, 58.2 mg, 1.45 mmol, 1.2 equiv) in dioxane abs. (1.4 mL), under an argon atmosphere. When hydrogen evolution subsides, a solution of 4,6-difluoro-pyrimidine (0.141 g, 1.21 mmol) in dioxane (0.4 mL) Is added. The resulting dark mixture is stirred for 1.5 h at rt, quenched by addition of MeOH (2 mL) and concentrated in vacuo. After addition of CH2Cl2, the resulting suspension is filtered and concentrated in vacuo. The residue is purified by silica gel column chromatography (CH2Cl2/Et2O, 90/10, then 85/15) to afford the title compound as a white solid: ES-MS: 204.0 [M+H]+; single peak at tR=4.96 min (System 2); Rf=0.30 (CH2Cl2/Et2O, 85/15).

Workup

  1. customquenched by addition of MeOH (2 mL)
  2. concentrationconcentrated in vacuo
  3. additionAfter addition of CH2Cl2
  4. filtrationthe resulting suspension is filtered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel column chromatography (CH2Cl2/Et2O, 90/10

Sources & evidence

ORD record
ord-d938ce83a85d4291b07a4f2181d2b472
Source dataset
uspto-grants-2010_01
Patent number
US07652022B2

Reaction notes

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