Diisopropylamine → 3,5-difluoro-4-[1-hydroxy-3-(1-trityl-1H-imidazol-4-yl)-propyl]benzonitrile

HRID 76879

반응식

HRID 76879 반응식
C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([F:22])[CH:21]=1)[C:17]#[N:18].[C:23]([N:42]1[CH:46]=[C:45]([CH2:47][CH2:48][CH:49]=[O:50])[N:44]=[CH:43]1)([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1.CCOC(C)=O>[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([F:22])[C:21]=1[CH:49]([OH:50])[CH2:48][CH2:47][C:45]1[N:44]=[CH:43][N:42]([C:23]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:46]=1)[C:17]#[N:18]

참가 물질

7

반응물 4

HCID 7912DiisopropylamineHCID 5872043,5-DifluorobenzonitrileHCID 114514283-(1-Tritylimidazol-4-YL) propionaldehydeHCID 178418339Butyllithium

생성물 1

HCID 668855153,5-difluoro-4-[1-hydroxy-3-(1-trityl-1H-imidazol-4-yl)-propyl]benzonitrile

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매3회HCID 8857Ethyl Acetate용매

반응 조건

온도
-78 °C

실험 절차

Diisopropylamine (0.53 mL, 3.75 mmol) is dissolved in 5 mL THF and cooled down to −78° C. To this is added n-BuLi (2.3 mL, 1.6M in hexanes). After 15 min, a solution of 3,5-difluorobenzonitrile (0.52 g, 3.75 mmol) and THF (5 mL) is added and the solution maintained at that temperature for 0.5 h before adding a solution of 3-(1-trityl-1H-imidazol-4-yl)propionaldehyde and THF (20 mL). After 2 h, the solution is diluted with EtOAc and quenched with saturated aqueous NH4Cl. The mixture is then partitioned between EtOAc and saturated aqueous NH4Cl. The organic is dried (Na2SO4) and evaporated. The residue is purified via flash column chromatography (EtOAc/hexanes 2:8→EtOAc) to give 3,5-difluoro-4-[1-hydroxy-3-(1-trityl-1H-imidazol-4-yl)-propyl]benzonitrile as a yellow powder. MS (ESI) m/z 506.2 (M+H).

후처리

  1. temperaturethe solution maintained at that temperature for 0.5 h
  2. waitAfter 2 h
  3. customquenched with saturated aqueous NH4Cl
  4. customThe mixture is then partitioned between EtOAc and saturated aqueous NH4Cl
  5. dry with materialThe organic is dried (Na2SO4)
  6. customevaporated
  7. customThe residue is purified via flash column chromatography (EtOAc/hexanes 2:8→EtOAc)

출처 및 근거

ORD 기록
ord-9e48427581204447a8ecfaad04250cfc
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835646B2

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