Water → 4-(6-fluoropyridin-3-yl)tetrahydro-2H-pyran-4-carbaldehyde

HRID 595927Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.[O:9]1[CH2:14][CH2:13][CH:12]([CH:15]=[O:16])[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Cs+].[Cs+].O.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:8][C:5]1[N:6]=[CH:7][C:2]([C:12]2([CH:15]=[O:16])[CH2:13][CH2:14][O:9][CH2:10][CH2:11]2)=[CH:3][CH:4]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 5-bromo-2-fluoropyridine (2.0 g, 11.36 mmol) in dioxane (35 mL) was added tetrahydro-2H-pyran-4-carbaldehyde (2.59 g, 22.73 mmol), Pd(OAc)2 (0.25 g, 1.14 mmol), cesium carbonate (7.41 g, 22.73 mmol), and water (10.24 μL, 0.57 mmol), xantphos (0.98 g, 1.70 mmol). The mixture was purged with nitrogen for 5 min, the resulting mixture was heated to 110° C. in an oil bath for 15 h. The mixture was diluted with ethyl acetate, and was washed with water, brine, dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography on silicagel (ISCO) eluting with 0-80% ethyl acetate in heptane to give 4-(6-fluoropyridin-3-yl)tetrahydro-2H-pyran-4-carbaldehyde (560 mg, 2.68 mmol, 23.5% yield) as red color oil. LCMS (m/z): 210 (MH+), 0.45 min.

Workup

customThe mixture was purged with nitrogen for 5 min
additionThe mixture was diluted with ethyl acetate
washwas washed with water, brine
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe residue was purified by flash column chromatography on silicagel (ISCO)
washeluting with 0-80% ethyl acetate in heptane

Sources & evidence

ORD record: ord-2c6ae76b0a164bd7a2b44de56cc7a056
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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