Ethanol → 2-(4-Bromo-2,6-difluorobenzyl)-6-(2,4-difluorophenyl)pyridine

HRID 1360692Notes

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 2-bromo-6-(4-bromo-2,6-difluorobenzyl)pyridine (from Step C above, 7.41 g, 20.53 mmol) in toluene (200 mL) was added (2,4-difluorophenyl)boronic acid (3.89 g, 24.63 mmol), tetrakis(triphenylphosphine)palladium (2.37 g, 2.05 mmol), ethanol (20 mL) and 2M Na2CO3 (20 mL). The reaction was heated to 90° C. until complete. The mixture was cooled to room temperature and concentrated. The crude residue was diluted with EtOAc/water (1:1) and washed with 1N HCl (2×), brine (3×), dried over MgSO4, and concentrated in vacuo. The crude material was purified via silica gel chromatography (hexanes/ethyl acetate) to give the title compound (7.23 g).

Workup

temperatureThe mixture was cooled to room temperature
concentrationconcentrated
additionThe crude residue was diluted with EtOAc/water (1:1)
washwashed with 1N HCl (2×), brine (3×)
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe crude material was purified via silica gel chromatography (hexanes/ethyl acetate)

Sources & evidence

ORD record: ord-482ddb4600564ed49432b5d08b7aae13
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879875B2

Reaction notes

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