2,4-Dichloropyridine → 4-(2-Chloropyridin-4-yloxy)-3-methylbenzenamine

HRID 450418Notes

Reaction equation

HRID 450418 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH3:9])[CH:3]=1.CC(C)([O-])C.[K+].[Cl:16][C:17]1[CH:22]=[C:21](Cl)[CH:20]=[CH:19][N:18]=1>CC(N(C)C)=O>[Cl:16][C:17]1[CH:22]=[C:21]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][C:4]=2[CH3:9])[CH:20]=[CH:19][N:18]=1

Participants

5

Reactant 3

HCID 335152,4-DichloropyridineHCID 760815-Amino-2-hydroxytolueneHCID 23665647Potassium tert-butoxide

Product 1

HCID 866196714-(2-Chloropyridin-4-yloxy)-3-methylbenzenamineYield 61.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A solution of 4-amino-2-methyl-phenol (4.25 g, 34.5 mmol) in dimethylacetamide (50 mL) was degassed in vacuo and blanketed with argon. Potassium tert-butoxide (5.0 g, 44.6 mmol) was added and the reaction mixture was de-gassed a second time and stirred at RT under argon for 30 min. 2,4-Dichloro-pyridine (4.6 g, 31.3 mmol) was added and the mixture was heated to 100° C. overnight. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography to give 4-(2-chloropyridin-4-yloxy)-3-methylbenzenamine (4.5 g, 56% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.21 (d, J=5.2 Hz, 1H), 6.75-6.80 (m, 3H), 6.45-6.50 (m, 2H), 5.15 (s, 2H), 1.92 (s, 3H); MS (ESI) m/z: 235.1 (M+H+).

Workup

  1. customthe reaction mixture was de-gassed a second time
  2. temperaturethe mixture was heated to 100° C. overnight
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-842d157dc36945aeb7dbaa7aad1afbf2
Source dataset
uspto-grants-2013_07
Patent number
US08486951B2

Reaction notes

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