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

HRID 76879

反応式

HRID 76879 の反応式
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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒3 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
-78 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-9e48427581204447a8ecfaad04250cfc
出典データセット
uspto-grants-2014_09
特許番号
US08835646B2

関連ノート

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