Trifluoroacetic acid → 2-Fluoro-5-(4-(methylthio)benzyl)pyridine

HRID 1621478ノート

反応式

HRID 1621478 の反応式
[F:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([C:10]2[CH:15]=[CH:14][C:13]([S:16][CH3:17])=[CH:12][CH:11]=2)O)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:10]2[CH:15]=[CH:14][C:13]([S:16][CH3:17])=[CH:12][CH:11]=2)=[CH:6][N:7]=1

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 59548286(6-Fluoropyridin-3-yl)(4-(methylthio)phenyl)methanol

生成物 1

HCID 595483662-Fluoro-5-(4-(methylthio)benzyl)pyridine収率 89%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of (6-fluoropyridin-3-yl)(4-(methylthio)phenyl)methanol (1.716 g, 6.88 mmol) in DCM (3.0 mL) was treated with trifluoroacetic acid (2.56 mL, 34.4 mmol) resulting in a green solution. The mixture was stirred for 5 min, and then triethylsilane (3.30 mL, 20.65 mmol) was added dropwise. The green color dissipated rapidly to give a straw colored solution, and a brief exotherm was observed (DCM started refluxing). The mixture was stirred for 30 min, and then extracted into DCM from saturated aqueous NaHCO3. The DCM extracts were dried (MgSO4) and purified by flash chromatography (5% to 7.5% EtOAc/hexane) to give 2-fluoro-5-(4-(methylthio)benzyl)pyridine (89% over 2 steps) as a colorless oil. 1H NMR (400 MHz, d6-DMSO) δ 8.15 (s, 1H); 7.81 (t, J=8.22 Hz, 1H); 7.20 (s, 4H); 7.10 (d, J=8.41 Hz, 1H); 3.94 (s, 2H); 2.44 (s, 3H). 19F NMR (376 MHz, d6-DMSO) δ −72.37 (s, 1F). m/z (ESI, +ve ion) 234.0 (M+H)+.

後処理

  1. customresulting in a green solution
  2. customto give a straw colored solution
  3. stirringThe mixture was stirred for 30 min
  4. extractionextracted into DCM from saturated aqueous NaHCO3
  5. dry with materialThe DCM extracts were dried (MgSO4)
  6. custompurified by flash chromatography (5% to 7.5% EtOAc/hexane)

出典と根拠

ORDレコード
ord-a220146ac5634ce8b4d7a0b10e46bc8d
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

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