Ethanol → 3-{[6-(2,4-Difluorophenyl)pyridin-2-yl]methyl}-4-fluorobenzonitrile

HRID 1360680Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([CH2:8][C:9]2[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=2[F:17])[C:12]#[N:13])[CH:5]=[CH:4][CH:3]=1.[F:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1B(O)O.C(O)C.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.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>[F:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[C:2]1[N:7]=[C:6]([CH2:8][C:9]2[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=2[F:17])[C:12]#[N:13])[CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of 3-[(6-bromopyridin-2-yl)methyl]-4-fluorobenzonitrile (from Step B above, 8.34 g, 28.6 mmol) in toluene (300 mL) was added (2,4-difluorophenyl)boronic acid (8.15 g, 34.4 mmol), tetrakis(triphenylphosphine)palladium (1.65 g, 1.40 mmol), ethanol (30 mL), and 2M Na2CO3 (30 mL). The resulting mixture was heated to 95° C. for 2 hours. The reaction was cooled to room temperature and filtered through celite and concentrated in vacuo. The crude residue was dissolved in EtOAc, washed with H2O, brine (2×), dried over MgSO4, and concentrated. The crude material was purified via silica gel chromatography (hexanes/ethyl acetate) to give the title compound as a white solid (7.03 g).

Workup

temperatureThe reaction was cooled to room temperature
filtrationfiltered through celite and
concentrationconcentrated in vacuo
dissolutionThe crude residue was dissolved in EtOAc
washwashed with H2O, brine (2×)
dry with materialdried over MgSO4
concentrationconcentrated
customThe crude material was purified via silica gel chromatography (hexanes/ethyl acetate)

Sources & evidence

ORD record: ord-cb49a1651c784edbb88282d0c77ccdd0
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879875B2

Reaction notes

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