Ethyl Acetate → 3-Methyl-5-nitro-2-[4-(trifluoromethyl)phenyl]pyridine

HRID 2406947Notes

Reaction equation

[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([N+:22]([O-:24])=[O:23])=[CH:17][N:16]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O.O1CCOCC1.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>[CH3:21][C:20]1[C:15]([C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:4][CH:5]=2)=[N:16][CH:17]=[C:18]([N+:22]([O-:24])=[O:23])[CH:19]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of 4-(trifluoromethyl)phenylboronic acid (285 mg, 1.5 mmol), 2-bromo-3-methyl-5-nitropyridine (216 mg, 1.0 mmol), and potassium carbonate (345 mg, 2.5 mmol) in water (1.5 mL) and dioxane (6 mL) was added tetrakis(triphenylphosphine)palladium(0) (40 mg, 0.035 mmol). The resulting mixture was stirred at 80° C. for 4.5 hours. The mixture was cooled to room temperature. Ethyl acetate was added and the mixture was washed with water, then brine, dried over sodium sulfate, filtered and concentrated. Purification by column chromatography gave 3-methyl-5-nitro-2-(4-(trifluoromethyl)phenyl)pyridine (223 mg, 79%). 1H NMR (400 MHz, CDCl3, δ): 9.35 (s, 1 H), 8.42 (s, 1 H), 7.77 (d, 2 H), 7.69 (d, 2 H), 2.51 (s, 3 H).

Workup

temperatureThe mixture was cooled to room temperature
washthe mixture was washed with water
dry with materialbrine, dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customPurification by column chromatography

Sources & evidence

ORD record: ord-af2aa79fed7749ba9a8ab47c6baaf1c7
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809342B2

Reaction notes

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