Dichloromethane → 2-fluoro-6-(tetrahydro-2H-pyran-4-yl)pyridin-3-ol

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Reaktionsgleichung

Br[C:2]1[N:7]=[C:6]([F:8])[C:5]([OH:9])=[CH:4][CH:3]=1.[O:10]1[CH2:15][CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[CH2:12][CH2:11]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl>O1CCOCC1.O.CO.C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C.[Pd]>[F:8][C:6]1[C:5]([OH:9])=[CH:4][CH:3]=[C:2]([CH:13]2[CH2:14][CH2:15][O:10][CH2:11][CH2:12]2)[N:7]=1

Komponenten

Reaktionsbedingungen

Temperatur: 110 °C

Versuchsvorschrift

6-Bromo-2-fluoropyridin-3-ol (3.67 g, 19.12 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4.02 g, 19.12 mmol), potassium phosphate (6.25 g, 29.4 mmol), and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (0.23 g, 0.33 mmol) were suspended in a mixture of dioxane (5 mL) and water (0.5 mL) and heated in the microwave to 110° C. for 20 min. The phases were allowed to settle and the organic evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to EtOAc gradient) gave the desired coupled material. It was dissolved in MeOH (60 mL) and DCM (30 mL) and treated with palladium (10% wt on carbon, 0.26 g, 0.24 mmol) and hydrogenated at 60 psi overnight. The mixture was filtered through a pad of celite and the filtrate evaporated under reduced pressure to give the desired 2-fluoro-6-(tetrahydro-2H-pyran-4-yl)pyridin-3-ol (1.92 g, 9.74 mmol, 50.9% yield). It was used without purification.

Aufarbeitung

customthe organic evaporated to dryness under reduced pressure
customPurification
customgave the
filtrationThe mixture was filtered through a pad of celite
customthe filtrate evaporated under reduced pressure

Quellen und Nachweise

ORD-Eintrag: ord-4720ffc985794605bc9bda7de4d82b1e
Quelldatensatz: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08883782B2

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