Sodium hydride → 4-Fluoro-2-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-pyridine

HRID 60665

반응식

HRID 60665 반응식
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][OH:10].[H-].[Na+].F[C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][N:15]=1>C1COCC1>[F:20][C:18]1[CH:17]=[CH:16][N:15]=[C:14]([O:10][CH2:9][CH2:8][O:7][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)[CH:19]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 27628382,4-DifluoropyridineHCID 41668332-(Oxan-2-yloxy)ethan-1-ol

생성물 1

HCID 1177296274-Fluoro-2-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-pyridine수율 52.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

2-(Tetrahydro-2H-pyran-2yl-oxy)ethanol (731 mg, 679 μL, 5.00 mmol) was suspended in anhydrous THF and NaH (60% dispersion in mineral oil, 240 mg, 6.0 mmol) was added portionwise, resulting in evolution of gas and the reaction stirred at room temp. After 15 min, a solution of 2,4-difluoropyridine (690 mg, 6.00 mmol) in anhydrous THF (2 mL) was slowly added. After stirring for 2 h, the reaction was partitioned between H2O and EtOAc. The organic layer was separated, and the aqueous extracted again with EtOAc. The combined organics were dried over MgSO4, concentrated in vacuo and subjected to FCC, eluting with 0-30% EtOAc/cyclohexane, to afford the title compound as a colourless oil (633 mg, 43%). LCMS (Method 3) Rt 3.57 min, m/z 264.2 [M+Na].

후처리

  1. customresulting in evolution of gas
  2. stirringAfter stirring for 2 h
  3. customthe reaction was partitioned between H2O and EtOAc
  4. customThe organic layer was separated
  5. extractionthe aqueous extracted again with EtOAc
  6. dry with materialThe combined organics were dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. washeluting with 0-30% EtOAc/cyclohexane

출처 및 근거

ORD 기록
ord-6c7d77c30cc7466483739d8d2b0b5680
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440974B2

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