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

HRID 595927ノート

反応式

HRID 595927 の反応式
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

参加物

8

反応物 5

HCID 962WaterHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27831685-Bromo-2-fluoropyridineHCID 9964078Tetrahydro-2H-pyran-4-carboxaldehyde

生成物 1

HCID 1180452994-(6-fluoropyridin-3-yl)tetrahydro-2H-pyran-4-carbaldehyde収率 23.6%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-2c6ae76b0a164bd7a2b44de56cc7a056
出典データセット
uspto-grants-2016_01
特許番号
US09242996B2

反応ノート

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