4-Aminophenol → 4-(2-(N-(2-morpholin-4-ylethyl)carbamoyl)pyridyloxy)aniline

HRID 2078553Notes

Reaction equation

HRID 2078553 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].Cl[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([C:22](=[O:32])[NH:23][CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:17]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[N:26]1([CH2:25][CH2:24][NH:23][C:22]([C:18]2([O:8][C:5]3[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=3)[CH:17]=[CH:16][CH:21]=[CH:20][NH:19]2)=[O:32])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 4034-AminophenolHCID 11430Potassium CarbonateHCID 236145794-chloro-2-(N-(2-morpholin-4-ylethyl)carbamoyl)pyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 667465414-(2-(N-(2-morpholin-4-ylethyl)carbamoyl)pyridyloxy)anilineYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A solution of 4-aminophenol (0.49 g, 4.52 mmol) and potassium tert-butoxide (0.53 g, 4.75 mol) in DMF (8 mL) was stirred at room temp. for 2 h, then was sequentially treated with 4-chloro-2-(N-(2-morpholin-4-ylethyl)carbamoyl)pyridine (1.22 g, 4.52 mmol) and K2CO3 (0.31 g, 2.26 mmol). The resulting mixture was heated at 75° C. overnight, cooled to room temp., and separated between EtOAc (25 mL) and a saturated NaCl solution (25 mL). The aqueous layer was back extracted with EtOAc (25 mL). The combined organic layers were washed with a saturated NaCl solution (3×25 mL) and concentrated under reduced pressure. The resulting brown solids were purified by column chromatography (58 g; gradient from 100% EtOAc to 25% MeOH/75% EtOAc) to afford 4-(2-(N-(2-morpholin-4-ylethyl)carbamoyl)pyridyloxy)aniline (1.0 g, 65%): TLC (10% MeOH/90% EtOAc) Rf 0.32.

Workup

  1. temperaturecooled to room temp.
  2. customseparated between EtOAc (25 mL)
  3. extractionThe aqueous layer was back extracted with EtOAc (25 mL)
  4. washThe combined organic layers were washed with a saturated NaCl solution (3×25 mL)
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting brown solids were purified by column chromatography (58 g; gradient from 100% EtOAc to 25% MeOH/75% EtOAc)

Sources & evidence

ORD record
ord-bd0c1056e3724525afb25e1f10d769c6
Source dataset
uspto-grants-2011_04
Patent number
US07928239B2

Reaction notes

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