1,4-Dioxane → Methyl 6-(2,6-difluoro-4-(methylthio)phenyl)-5-fluoropicolinate

HRID 1499551Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[C:4]([F:10])[C:3]=1B1OC(C)(C)C(C)(C)O1.Br[C:21]1[N:26]=[C:25]([C:27]([O:29][CH3:30])=[O:28])[CH:24]=[CH:23][C:22]=1[F:31].CCN(C(C)C)C(C)C.O1CCOCC1>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O>[F:10][C:4]1[CH:5]=[C:6]([S:8][CH3:9])[CH:7]=[C:2]([F:1])[C:3]=1[C:21]1[N:26]=[C:25]([C:27]([O:29][CH3:30])=[O:28])[CH:24]=[CH:23][C:22]=1[F:31]

Participants

Conditions

Temperature: 120 °C

Procedure

In a sealed tube, a mixture of 2-[2,6-difluoro-4-(methylthio)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.00 g, 3.49 mmol), methyl 6-bromo-5-fluoropyridine-2-carboxylate (1.23 g, 5.24 mmol) and DIPEA (1.83 mL, 10.5 mmol) in a mixed solvent of 1,4-dioxane (15 mL) and water (0.51 mL) was stirred and flushed with nitrogen bubbles for 5 min. before bis(tri-tert-butylphosphine)palladium (360 mg, 0.70 mmol) was added. The reaction mixture was heated at 120° C. for 30 min. After cooling, the reaction mixture was filtered, and the filter was washed with THF. The filtrate was concentrated and then purified by silica gel column chromatography using CombiFlash® (0 to 20% EtOAc in hexanes) to give the sub-title compound as powder (442 mg, 40%). LCMS calc. for C14H11F3NO2S (M+H)+: m/z=314.1. Found: 314.2.

Workup

additionwas added
temperatureAfter cooling
filtrationthe reaction mixture was filtered
washthe filter was washed with THF
concentrationThe filtrate was concentrated
custompurified by silica gel column chromatography

Sources & evidence

ORD record: ord-536c063def5a4555ae4a97bea276df49
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09200004B2

Reaction notes

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