Citric Acid → 2-(4-Fluoro-phenyl)-3-oxo-3-(6-trifluoromethyl-pyridin-2-yl)-propionitrile

HRID 8223

反応式

HRID 8223 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].ClC1C=CC(S[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[N:32]=2)=[O:30])=CC=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:29](=[O:30])[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:39])([F:38])[F:40])[N:32]=2)[C:9]#[N:10])=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 311Citric AcidHCID 68016Benzeneacetonitrile, 4-fluoro-HCID 3251421Potassium bis(trimethylsilyl)amideHCID 41561066-trifluoromethyl-pyridine-2-carbothioic acid S-(4-chloro-phenyl) ester

生成物 1

HCID 219926412-(4-Fluoro-phenyl)-3-oxo-3-(6-trifluoromethyl-pyridin-2-yl)-propionitrile収率 66%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of 4-fluorophenylacetonitrile (0.12 mL, 1.0 mmol) in dry tetrahydrofuran (2 mL) is treated dropwise with potassium bis(trimethylsilyl)amide (0.5 M toluene, 3.0 mL, 1.5 mmol) at 0° C. under an atmosphere of nitrogen. The mixture is stirred 10 min then 6-trifluoromethyl-pyridine-2-carbothioic acid S-(4-chloro-phenyl) ester is added all at once. The mixture is allowed to warn to room temperature then warmed to reflux for 10 min, at which time the reaction is complete by TLC (methylene chloride). The mixture is allowed to cool then poured into 10% citric acid and extracted into methylene chloride. The methylene chloride solution is dried over magnesium sulfate and concentrated in vacuo. The residue is purified on a silica gel cartridge prepared with hexane then eluted with methylene chloride to yield 204 mg (66%) 2-(4-fluoro-phenyl)-3-oxo-3-(6-trifluoromethyl-pyridin-2-yl)-propionitrile. MS ES− m/z 307 (M−1).

後処理

  1. customto warn to room temperature
  2. temperaturethen warmed
  3. temperatureto reflux for 10 min, at which time the reaction
  4. temperatureto cool
  5. extractionextracted into methylene chloride
  6. dry with materialThe methylene chloride solution is dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified on a silica gel cartridge
  9. customprepared with hexane
  10. washthen eluted with methylene chloride

出典と根拠

ORDレコード
ord-93bcccec9d1e4801a4fde7f976f24c31
出典データセット
uspto-grants-2006_08
特許番号
US07087626B2

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