2,6-Difluoropyridine-4-boronic acid → 2,6-Difluoro-4-(oxetan-3-yl)pyridine

HRID 57969

반응식

HRID 57969 반응식
[F:1][C:2]1[CH:7]=[C:6](B(O)O)[CH:5]=[C:4]([F:11])[N:3]=1.Cl.N[C@@H]1CC[CH2:17][CH2:16][C@H:15]1[OH:20].C[Si](C)(C)N[Si](C)(C)C.[Na].IC1COC1>C(O)(C)C.CCO.[Ni](I)I>[F:1][C:2]1[CH:7]=[C:6]([CH:16]2[CH2:15][O:20][CH2:17]2)[CH:5]=[C:4]([F:11])[N:3]=1

참가 물질

8

반응물 4

HCID 27627472,6-Difluoropyridine-4-boronic acidHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-HCID 133566863-IodooxetaneHCID 45051731Sodium hexamethyidisilazane

생성물 1

HCID 867071522,6-Difluoro-4-(oxetan-3-yl)pyridine수율 390%

시약·촉매·용매 3

HCID 26038Nickel(II) iodide촉매HCID 702Ethanol용매HCID 3776Isopropanol용매2회

반응 조건

온도
100 °C

실험 절차

(2,6-difluoro-4-pyridyl)boronic acid (4.0004 mmol; 635.67 mg), Nickel(II) iodide (0.12001 mmol; 37.503 mg), Trans-2-aminocyclohexanol hydrochloride (0.12001 mmol; 18.382 mg), and Sodium hexamethyldisilazane (4.0004 mmol; 748.56 mg) were weighed into a CEM microwave vial. The mixture was capped then placed under a nitrogen atmosphere. Isopropanol (15 mL) was added and the mixture was stirred under nitrogen for 5 minutes. 3-Iodooxetane (2.0002 mmol; 368 mg) in Isopropanol (1.5 mL) was then added. The vial was heated at 100° C. under microwave for 20 minutes. The mixture was diluted with EtOH (15 mL) and filtered through Celite. The filter cake was washed with EtOH (2×10 mL). The mixture was concentrated and the residue was purified on silica eluted with 0 to 50% EtOAc in DCM to afford 2,6-difluoro-4-(oxetan-3-yl)pyridine (80.1 mg, 23%).

후처리

  1. customThe mixture was capped
  2. filtrationfiltered through Celite
  3. washThe filter cake was washed with EtOH (2×10 mL)
  4. concentrationThe mixture was concentrated
  5. customthe residue was purified on silica
  6. washeluted with 0 to 50% EtOAc in DCM

출처 및 근거

ORD 기록
ord-fae1389599f34c52b589270d8994c3bd
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434725B2

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