Potassium Carbonate → 5-(5-Chloropyridin-3-yloxy)-2,4-difluorobenzenamine

HRID 1711616Notes

Reaction equation

[NH2:1][C:2]1[C:3]([F:10])=[CH:4][C:5]([F:9])=[C:6]([OH:8])[CH:7]=1.CC(C)([O-])C.[K+].[Cl:17][C:18]1[CH:19]=[N:20][CH:21]=[C:22](Cl)[CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[Cl:17][C:18]1[CH:23]=[C:22]([O:8][C:6]2[C:5]([F:9])=[CH:4][C:3]([F:10])=[C:2]([NH2:1])[CH:7]=2)[CH:21]=[N:20][CH:19]=1

Participants

Conditions

Temperature: 190 °C

Procedure

To a solution of 5-amino-2,4-difluorophenol (0.3 g, 2.07 mmol) in DMSO (2 mL) was added potassium t-butoxide (0.23 g, 2.07 mmol) at RT. After stirring for 1 h, 3,5-dichloropyridine (0.37 g, 2.5 mmol) and potassium carbonate (0.14 g, 1 mmol) were added and the mixture was heated to 190° C. for 1 h in microwave reactor. Water (30 mL) was added, and the product was extracted with EtOAc (2×35 mL) and the combined organic layers were washed with brine solution, dried (Na2SO4), concentrated in vacuo and purified by chromatography (EtOAc/hexane) to afford 5-(5-chloropyridin-3-yloxy)-2,4-difluorobenzenamine (0.35 g, 66% yield) as a solid. 1H NMR (400 MHz, Acetone-d6) δ 8.33-8.30 (m, 2H), 7.44 (t, J=2.4 Hz, 1H), 7.13 (t, J=10.8 Hz, 1H), 6.78 (t, J=8.4 Hz, 1H), 4.85 (brs, 2H); MS (ESI) m/z: 257.0 (M+H+).

Workup

extractionthe product was extracted with EtOAc (2×35 mL)
washthe combined organic layers were washed with brine solution
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
custompurified by chromatography (EtOAc/hexane)

Sources & evidence

ORD record: ord-435b920e38dd4bc8a8e348a4a7554058
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07790756B2

Reaction notes

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