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

HRID 1427451Notes

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, 1H), 8.42 (s, 1H), 7.77 (d, 2H), 7.69 (d, 2H), 2.51 (s, 3H).

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-8e96afd0e01c4b57b4e69d613eb426e9
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933104B2

Reaction notes

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