Imidazole → 3-((5-Bromo-2-methoxyphenyl)(tert-butyldimethylsilyloxy)methyl)-2,6-difluoropyridine

HRID 335902Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([CH:8]([C:10]2[C:11]([F:17])=[N:12][C:13]([F:16])=[CH:14][CH:15]=2)[OH:9])[CH:7]=1.N1C=CN=C1.[C:25]([Si:29](Cl)([CH3:31])[CH3:30])([CH3:28])([CH3:27])[CH3:26].O>CN(C=O)C.C(OCC)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([CH:8]([O:9][Si:29]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:31])[CH3:30])[C:10]2[C:11]([F:17])=[N:12][C:13]([F:16])=[CH:14][CH:15]=2)[CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

(5-Bromo-2-methoxyphenyl)(2,6-difluoropyridin-3-yl)methanol (13.77 g, 41.7 mmol) and imidazole (3.41 g, 50.1 mmol) were dissolved in dry DMF (20 mL) under nitrogen. t-Butyl(chloro)dimethylsilane (6.92 g, 45.9 mmol) was added and the solution heated to 70° C. After 1 hour the mixture was cooled to RT. Water (200 mL) and diethyl ether (200 mL) were added and the phases mixed and separated. The organic was washed with water (200 mL) one more time then dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to 1:1 DCM: hexane gradient) gave 3-((5-bromo-2-methoxyphenyl)(tert-butyldimethylsilyloxy)methyl)-2,6-difluoropyridine as a thick oil that solidified on standing.

Workup

temperatureAfter 1 hour the mixture was cooled to RT
additionthe phases mixed
customseparated
washThe organic was washed with water (200 mL) one more time
dry with materialthen dried with magnesium sulfate
customevaporated to dryness under reduced pressure
customPurification

Sources & evidence

ORD record: ord-177acd573d094f4ead0f1d968a405d05
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883782B2

Reaction notes

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