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

HRID 1768283Notes

Reaction equation

HRID 1768283 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 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-e566e954ccd04d60afc4de21e6a0d116
Source dataset
uspto-grants-2007_06
Patent number
US07235576B1

Reaction notes

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