Sodium Carbonate → 2-Chloro-4-methyl-6-(4-trifluoromethyl-phenyl)-pyridine

HRID 2427870Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.[F:10][C:11]([F:22])([F:21])[C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.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>[Cl:9][C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([C:15]2[CH:16]=[CH:17][C:12]([C:11]([F:22])([F:21])[F:10])=[CH:13][CH:14]=2)[N:3]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a degassed solution of 2-bromo-6-chloro-4-methyl-pyridine (900 mg, 4.37 mmol), 4-trifluoromethylbenzeneboronic acid (830 mg, 4.37 mmol), 2N Na2CO3 (4 mL) in DME (40 mL) was added tetrakis(triphenylphosphine)palladium (320 mg, 0.3 mmol) under argon. The mixture was heated to 55° C. for 5 h, cooled to room temperature, diluted with water, and extracted with methylene chloride (3×). The organic solution was washed with brine, dried over Na2SO4, and concentrated. The residue was purified by column chromatography on silica gel (10-25% methylene chloride in heptane) to give the product as an off white solid (800 mg, 68%). 1H NMR (300 MHz, CDCl3) δ 8.09 (d, J=7.91 Hz, 2H), 7.71 (d, J=8.29 Hz, 2H), 7.49 (s, 1H), 7.16 (s, 1H), 2.43 (s, 3H). MS m/e 272.1 (M+H).

Workup

temperaturecooled to room temperature
extractionextracted with methylene chloride (3×)
washThe organic solution was washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated
customThe residue was purified by column chromatography on silica gel (10-25% methylene chloride in heptane)

Sources & evidence

ORD record: ord-3acb29a0847d4206a2ae15795f17a837
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07968725B2

Reaction notes

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