4-Aminophenol → 4-(2-Chloro-pyridin-4-yloxy)-phenylamine

HRID 1993538Notes

Reaction equation

HRID 1993538 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].[H][H].[Cl:13][C:14]1[CH:19]=[C:18]([N+]([O-])=O)[CH:17]=[CH:16][N:15]=1>O1CCOCC1>[Cl:13][C:14]1[CH:19]=[C:18]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[CH:17]=[CH:16][N:15]=1

Participants

6

Reactant 4

HCID 4034-AminophenolHCID 24758Sodium hydrideHCID 7351522-Chloro-4-nitropyridineHCID 178418361HCID 178418361, compound

Product 1

HCID 578334304-(2-Chloro-pyridin-4-yloxy)-phenylamine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

4-Amino-phenol (1.05g, 9.40 mmol, 1.1 equiv) is added in one portion to a suspension of NaH (60% free-flowing powder moistened with oil, 0.513 g, 12.8 mmol, 1.5 equiv) in dioxane abs. (6.5 mL), under an argon atmosphere. When hydrogen evolution subsides, a solution of 2-chloro-4-nitropyridine (1.35 g, 8.54 mmol) in dioxane (6 mL) is added. The resulting dark mixture is heated to 100° C. (oil bath temperature) for 70.5 h, allowed to cool to rt, quenched by addition of MeOH and partially concentrated in vacuo. The oily residue is dissolved in CH2Cl2/MeOH (80/20) and filtered through a glass sintered funnel containing silica gel (18 g), eluting with CH2Cl2/MeOH (90/10). The filtrate is partially concentrated in vacuo, diluted with CH2Cl2/MeOH (90/10) and purified by silica gel (70 g) column chromatography (CH2Cl2/Et2O, 90/10, then 85/15). A second column chromatography purification affords the title compound as a yellow solid: ES-MS: 221.1 [M+H]+; single peak at tR=6.56 min (System 2); Rf=0.27 (CH2Cl2/Et2O, 80/20).

Workup

  1. temperatureto cool to rt
  2. customquenched by addition of MeOH
  3. concentrationpartially concentrated in vacuo
  4. dissolutionThe oily residue is dissolved in CH2Cl2/MeOH (80/20)
  5. filtrationfiltered through a glass
  6. additioncontaining silica gel (18 g)
  7. washeluting with CH2Cl2/MeOH (90/10)
  8. concentrationThe filtrate is partially concentrated in vacuo
  9. additiondiluted with CH2Cl2/MeOH (90/10)
  10. custompurified by silica gel (70 g) column chromatography (CH2Cl2/Et2O, 90/10
  11. customA second column chromatography purification

Sources & evidence

ORD record
ord-96932ee3f2044153bb870bff57baf367
Source dataset
uspto-grants-2010_01
Patent number
US07652022B2

Reaction notes

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