Methyl iodide → 2-Chloro-4-fluoro-3-methylbenzonitrile

HRID 245048

반응식

HRID 245048 반응식
[CH:1](NC(C)C)(C)C.C([Li])CCC.[Li+].CC([N-]C(C)C)C.[Cl:21][C:22]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:23]=1[C:24]#[N:25].IC.[Cl-].[NH4+]>C1COCC1.O>[Cl:21][C:22]1[C:29]([CH3:1])=[C:28]([F:30])[CH:27]=[CH:26][C:23]=1[C:24]#[N:25]

참가 물질

9

반응물 6

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 1090002-Chloro-4-fluorobenzonitrileHCID 2724682Lithium diisopropylamideHCID 178418339Butyllithium

생성물 1

HCID 445509712-Chloro-4-fluoro-3-methylbenzonitrile수율 74%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-5 °C

실험 절차

To a solution of diisopropylamine (474 mL, 3.35 mol) in anhydrous THF (5.8 L) at −5° C. under a nitrogen atmosphere is added dropwise 2.5 M n-butyllithium in hexanes (1.24 L, 3.10 mol) over 3 h and the resulting mixture is stirred at −5° C. for one additional hour. The LDA solution is added dropwise to a solution of 2-chloro-4-fluoro-benzonitrile (400 g, 2.58 mol) in anhydrous THF (5.8 L) at −70° C. over 6 h and then stirred at −70° C. overnight. Iodomethane (643 mL, 10.32 mol) is added dropwise over 2.5 h and the temperature is raised to −5° C. for 17 h. Saturated aqueous ammonium chloride (3 L) is added. The solution is diluted with water (3.5 L) and extracted with diethyl ether (2×2 L). The organic phases are separated, combined, dried over anhydrous sodium sulfate, filtered, and concentrated to afford a black solid. The solid is purified through a silica gel pad eluting with EtOAc/hexanes (1/40) to obtain the title compound (323 g, 74%). 1H NMR (300 MHz, CDCl3) δ 7.08 (dd, J=8.6, 8.6 Hz, 1H), 7.54 (dd, J=8.6, 5.6 Hz, 1H), 2.36 (d, J=2.4 Hz, 3H).

후처리

  1. stirringstirred at −70° C. overnight
  2. temperaturethe temperature is raised to −5° C. for 17 h
  3. extractionextracted with diethyl ether (2×2 L)
  4. customThe organic phases are separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a black solid
  9. customThe solid is purified through a silica gel pad
  10. washeluting with EtOAc/hexanes (1/40)

출처 및 근거

ORD 기록
ord-6c9c8b01b8a145358af8f58549edc534
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658693B2

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