Diethyl Ether → 4,4-Difluoro-1-[6-(1-hydroxy-1-methyl-ethyl)-pyridin-3-yl]-cyclohexanecarbonitrile

HRID 512159노트

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HRID 512159 반응식
[C:1]([C:4]1[N:9]=[CH:8][C:7]([C:10]2([C:18]#[N:19])[CH2:15][CH2:14][C:13]([F:17])([F:16])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:20][Mg]Br.CCOCC>C1COCC1>[F:17][C:13]1([F:16])[CH2:12][CH2:11][C:10]([C:7]2[CH:8]=[N:9][C:4]([C:1]([OH:3])([CH3:20])[CH3:2])=[CH:5][CH:6]=2)([C:18]#[N:19])[CH2:15][CH2:14]1

참가 물질

5

반응물 3

HCID 3283Diethyl EtherHCID 867161801-(6-Acetyl-pyridin-3-yl)-4,4-difluoro-cyclohexanecarbonitrileHCID 178418573HCID 178418573, 화합물

생성물 1

HCID 867161824,4-Difluoro-1-[6-(1-hydroxy-1-methyl-ethyl)-pyridin-3-yl]-cyclohexanecarbonitrile수율 48%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-50 °C

실험 절차

A solution of 1-(6-acetyl-pyridin-3-yl)-4,4-difluoro-cyclohexanecarbonitrile (17 mg, 0.064 mmol) in THF (1.2 mL) was cooled at −50° C. and treated with a 3.0 M solution of methylmagnesium bromide in ether (110 μL, 0.32 mmol). After stirring at −50° C. for 3 hours, the reaction was quenched by adding saturated aqueous ammonium chloride (5 mL) and stirred at room temperature for a few minutes. AcOEt (5 mL) was added and the biphasic mixture was stirred vigorously for a few seconds. The layers were separated and the aqueous layer was extracted again with AcOEt (5 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was then purified by preparative TLC, eluting with 60% AcOEt in hexanes to afford 4,4-difluoro-1-[6-(1-hydroxy-1-methyl-ethyl)-pyridin-3-yl]-cyclohexanecarbonitrile as a colorless oil (8.7 mg, 48%). LC-MS (m/z) 280.0 (MH+); tR=1.11.

후처리

  1. customthe reaction was quenched
  2. additionby adding saturated aqueous ammonium chloride (5 mL)
  3. stirringstirred at room temperature for a few minutes
  4. additionAcOEt (5 mL) was added
  5. stirringthe biphasic mixture was stirred vigorously for a few seconds
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted again with AcOEt (5 mL)
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was then purified by preparative TLC
  12. washeluting with 60% AcOEt in hexanes

출처 및 근거

ORD 기록
ord-63eae451ce874ba694a323e9005689db
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102591B2

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