Ethanol → Ethyl 3-fluoro-5-hydroxypicolinate

HRID 2277300Notes

Reaction equation

[Si]([O:18][C:19]1[CH:20]=[C:21]([F:26])[C:22](Cl)=[N:23][CH:24]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C.[CH2:34]([OH:36])[CH3:35].CN([CH:40]=[O:41])C>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[F:26][C:21]1[C:22]([C:40]([O:36][CH2:34][CH3:35])=[O:41])=[N:23][CH:24]=[C:19]([OH:18])[CH:20]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 5-((tert-butyl(diphenyl)silyl)oxy)-2-chloro-3-fluoropyridine (29.5 g), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (5.59 g), triethylamine (10.7 mL), ethanol (300 mL) and DMF (300 mL) was stirred overnight at 80° C. under a carbon monoxide atmosphere. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The combined organic layer were washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (30.8 g) as a mixture with DMF.

Workup

extractionthe mixture was extracted with ethyl acetate
washThe combined organic layer were washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
customthe solvent was evaporated under reduced pressure
customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record: ord-6e9241dba6cc43e586c897bb30a657cd
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133129B2

Reaction notes

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