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

HRID 335953Notes

Reaction equation

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

Participants

Conditions

Temperature: 110 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-4720ffc985794605bc9bda7de4d82b1e
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883782B2

Reaction notes

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