2,4-Dichloropyridine → 4-(2-Chloropyridin-4-yloxy)-2-fluorobenzenamine

HRID 1098541Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[NH2:8].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:9][C:4]2[CH:5]=[CH:6][C:7]([NH2:8])=[C:2]([F:1])[CH:3]=2)[CH:20]=[CH:19][N:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A suspension of 3-fluoro-4-aminophenol (8.0 g, 63.0 mmol) in dimethylacetamide (80 mL) was de-gassed in vacuo and treated with potassium tert-butoxide (7.3 g, 65 mmol). The resultant mixture was stirred at RT for 30 min. 2,4-Dichloropyridine (8 g, 54 mmol) was added and the mixture was heated to 80° C. for 12 h. The solvent was removed under reduced pressure to give a residue which was partitioned between water and EtOAc (3×100 mL). The organic layers were washed with saturated brine, dried (MgSO4), concentrated in vacuo and purified by silica gel column chromatography to give 4-(2-chloro-pyridin-4-yloxy)-2-fluoro-phenylamine (11 g, 86% yield). 1H NMR (300 MHz, DMSO-d6), δ 8.24 (d, J=5.7 Hz, 1 H), 7.00 (dd, J=9.0, 2.7 Hz, 1 H), 6.89-6.73 (m, 4 H), 5.21 (br s, 2 H); MS (ESI) m/z: 239.2 (M+H+).

Workup

customwas de-gassed in vacuo
customThe solvent was removed under reduced pressure
customto give a residue which
customwas partitioned between water and EtOAc (3×100 mL)
washThe organic layers were washed with saturated brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
custompurified by silica gel column chromatography

Sources & evidence

ORD record: ord-54e7c728a26b49999c8a21c44911d891
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143293B2

Reaction notes

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