2,4-Dichloropyridine → 3-Chloro-4-(2-chloropyridin-4-yloxy)benzenamine

HRID 450420Notes

Reaction equation

CC([O-])(C)C.[K+].[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[C:10]([Cl:15])[CH:9]=1.[Cl:16][C:17]1[CH:22]=[C:21](Cl)[CH:20]=[CH:19][N:18]=1>CN(C=O)C.O.CCOC(C)=O>[Cl:15][C:10]1[CH:9]=[C:8]([NH2:7])[CH:13]=[CH:12][C:11]=1[O:14][C:21]1[CH:20]=[CH:19][N:18]=[C:17]([Cl:16])[CH:22]=1

Participants

Conditions

Temperature: 90 °C

Procedure

KOtBu (1.016 g, 9.05 mmol) was added to a solution of 4-amino-2-chlorophenol (1.00 g, 6.97 mmol) in DMF (35 ml) at RT and the resultant mixture was stirred 45 min. 2,4-Dichloropyridine (1.340 g, 9.05 mmol) was then added and the reaction was stirred with heating at 90° C. overnight. The reaction was cooled to RT and diluted generously with H2O and EtOAc. The layers were separated. The aqueous was extracted with EtOAc (3×). The combined organics were washed with H2O (1×) and brine (2×), dried (MgSO4), concentrated in vacuo and purified by silica gel chromatography (EtOAc/hexanes) to afford 3-chloro-4-(2-chloropyridin-4-yloxy)benzenamine (0.89 g, 50% yield) as a waxy yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 8.24 (d, J=5.7 Hz, 1H), 7.02 (d, J=8.7 Hz, 1H), 6.87-6.82 (m, 2H), 6.73-6.72 (m, 1H), 6.58-6.56 (m, 1H), 5.50 (br s, 2H); MS (ESI) m/z: 254.9 (M+H+); 256.9 (M+2+H+).

Workup

temperatureThe reaction was cooled to RT
customThe layers were separated
extractionThe aqueous was extracted with EtOAc (3×)
washThe combined organics were washed with H2O (1×) and brine (2×)
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
custompurified by silica gel chromatography (EtOAc/hexanes)

Sources & evidence

ORD record: ord-228e9b5b6cec4209aae604119666eef0
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486951B2

Reaction notes

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