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

HRID 595927노트

반응식

HRID 595927 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

반응 조건

온도
110 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-2c6ae76b0a164bd7a2b44de56cc7a056
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242996B2

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