Cesium carbonate → 5-bromo-2-(2-chloropyridin-4-yloxy)-N,N-diethylbenzamide

HRID 1970263Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][N:3]=1.[Br:9][C:10]1[CH:11]=[CH:12][C:13]([OH:23])=[C:14]([CH:22]=1)[C:15]([N:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[O:16].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[Br:9][C:10]1[CH:11]=[CH:12][C:13]([O:23][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[CH:7]=2)=[C:14]([CH:22]=1)[C:15]([N:17]([CH2:18][CH3:19])[CH2:20][CH3:21])=[O:16]

Participants

Conditions

Temperature: 100 °C

Procedure

2-Chloro-4-fluoropyridine (0.242 g, 1.837 mmol) was added to a mixture of 5-bromo-N,N-diethyl-2-hydroxybenzamide (0.500 g, 1.837 mmol) and cesium carbonate (1.197 g, 3.67 mmol) in acetonitrile (10.0 mL). The mixture stirred at 100° C. for 8 h. The reaction mixture was partitioned between ethyl acetate and water. The aqueous phase was separated and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to afford a brown oil. This oil was purified via column chromatography on silica gel (RediSep 80 g column, gradient elution with 0-50% ethyl acetate-hexane) to afford 5-bromo-2-(2-chloropyridin-4-yloxy)-N,N-diethylbenzamide as a thick, yellow oil. MS m/z=383.0 [M+H]+. Calcd for C16H16BrClN2O2: 382.0.

Workup

customThe reaction mixture was partitioned between ethyl acetate and water
customThe aqueous phase was separated
extractionextracted with ethyl acetate
washThe combined organic phases were washed with brine
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated
customto afford a brown oil
customThis oil was purified via column chromatography on silica gel (RediSep 80 g column, gradient elution with 0-50% ethyl acetate-hexane)

Sources & evidence

ORD record: ord-360d46d15d2f40c3af7464f922160faa
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426447B2

Reaction notes

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