(Diethylamino)sulfur trifluoride → 4-Chloro-6-(fluoromethyl)-5-methylpyrimidine

HRID 2401216ノート

反応式

HRID 2401216 の反応式
CCN(S(F)(F)[F:7])CC.[Cl:10][C:11]1[N:16]=[CH:15][N:14]=[C:13]([CH2:17]O)[C:12]=1[CH3:19]>ClCCl>[Cl:10][C:11]1[C:12]([CH3:19])=[C:13]([CH2:17][F:7])[N:14]=[CH:15][N:16]=1

参加物

4

反応物 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 86762586(6-Chloro-5-methylpyrimidin-4-yl)methanol2 回

生成物 1

HCID 866733784-Chloro-6-(fluoromethyl)-5-methylpyrimidine収率 74.9%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
-78 °C

実験手順

DAST (1.5 mL, 11.35 mmol) was added to dichloromethane (DCM) (64 mL), cooled to −78° C. and treated dropwise with a solution of (6-chloro-5-methyl-4-pyrimidinyl)methanol (Intermediate 50, 1.70 g, 10.72 mmol) in DCM (24 mL) under argon. The resulting mixture was allowed to warm to room temperature and stirred for 3 hours. The reaction was quenched by adding water (45 ml) and extracted with DCM (×2). The DCM layers were separated, combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (SP4, 40+M) eluting with a gradient of 0-50% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a yellow oil (1.29 g) m/z (ES+) 161 (M+1), title compound is 42% pure by LCMS. Also contains 4-bromo-6-(fluoromethyl)-5-methylpyrimidine, m/z (ES+) 205, 207 (M+1) (44% by LCMS)

後処理

  1. temperatureto warm to room temperature
  2. customThe reaction was quenched
  3. additionby adding water (45 ml)
  4. extractionextracted with DCM (×2)
  5. customThe DCM layers were separated
  6. customdried under magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by column chromatography (SP4, 40+M)
  9. washeluting with a gradient of 0-50% ethyl acetate and iso-hexane
  10. additionProduct containing fractions
  11. customevaporated under reduced pressure

出典と根拠

ORDレコード
ord-0ac1a5344e2f4ebe9549d288aed52367
出典データセット
uspto-grants-2014_08
特許番号
US08796283B2

反応ノート

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