2,6-Dibromopyridine → 3-[(6-Bromopyridin-2-yl)methyl]-4-fluorobenzonitrile

HRID 1360679Notes

Reaction equation

Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[F:11])[C:6]#[N:7].[Br:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15](Br)[N:14]=1>C1COCC1.[Zn].C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:12][C:13]1[N:14]=[C:15]([CH2:2][C:3]2[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=2[F:11])[C:6]#[N:7])[CH:16]=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 3-(bromomethyl)-4-fluorobenzonitrile (from Step A above, 17.7 g, 83.3 mmol) in THF was cooled to 0° C. and then 160 mL of Zn/THF solution (124.4 mmol) was added. After stirring at 0° C. for 45 minutes, the reaction was stirred at ambient temperature for an additional 20 minutes. To this reaction mixture was added 2,6-dibromo pyridine (19.73 g, 83.3 mmol) and tetrakis(triphenylphosphine)palladium (5.00 g, 4.30 mmol), and heated to 90° C. for 1.5 hours until the reaction was complete by TLC. The reaction was cooled to room temperature, filtered through celite, and concentrated. The crude residue was purified via silica gel chromatography (hexanes/methylene chloride) to give the title compound (8.34 g).

Workup

stirringthe reaction was stirred at ambient temperature for an additional 20 minutes
temperatureheated to 90° C. for 1.5 hours until the reaction
temperatureThe reaction was cooled to room temperature
filtrationfiltered through celite
concentrationconcentrated
customThe crude residue was purified via silica gel chromatography (hexanes/methylene chloride)

Sources & evidence

ORD record: ord-59e3205dc6134386b248a1d7774a383e
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879875B2

Reaction notes

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