4-Aminophenol → 4-(2-Methyl-4-pyridinyloxy)aniline
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Cl[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([CH3:16])[CH:11]=1.CC(C)([O-])C.[K+].O>CN1C(=O)N(C)CCC1>[CH3:16][C:12]1[CH:11]=[C:10]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[CH:15]=[CH:14][N:13]=1Participants
Conditions
- Temperature
- 100 °C
Procedure
To a solution of 4-aminophenol (3.6 g, 32.8 mmol) and 4-chloropicoline (5.0 g, 39.3 mmol) in anh DMPU (50 mL) was added potassium tert-butoxide (7.4 g, 65.6 mmol) in one portion. The reaction mixture was heated at 100° C. with stirring for 18 h, then was allowed to cool to room temp. The resulting mixture was poured into water (200 mL) and extracted with EtOAc (3×150 mL). The combined extracts were sequentially washed with water (3×100 mL) and a saturated NaCl solution (2×100 mL), dried (Na2SO4), and concentrated in vacuo. The resulting oil was purified by flash chromatography (50% EtOAc/50% hexane) to afford the desired product as a yellow oil (0.7 g, 9%): CI-MS m/z 201 ((M+H)+). A14c. General Method for Substituted Aniline Synthesis via Nucleophilic Aromatic Substitution using a Halopyridine
Workup
- temperatureto cool to room temp
- extractionextracted with EtOAc (3×150 mL)
- washThe combined extracts were sequentially washed with water (3×100 mL)
- dry with materiala saturated NaCl solution (2×100 mL), dried (Na2SO4)
- concentrationconcentrated in vacuo
- customThe resulting oil was purified by flash chromatography (50% EtOAc/50% hexane)
Sources & evidence
- ORD record
- ord-560f9cf896d34b19a5bc25d18ed75c16
- Source dataset
- uspto-grants-2009_04
- Patent number
- US07517880B2
Reaction notes
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