2-Iodotoluene → [4-(2-Methylphenyl)-4-oxo-1-butyl]piperidine

HRID 1723876

Reaktionsgleichung

Reaktionsgleichung von HRID 1723876
I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH3:8].[N:9]1([CH2:15][CH2:16][CH2:17][C:18]#N)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C(O)(C(F)(F)F)=[O:21].CC#N>CCOCC.C(Cl)Cl>[CH3:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:18](=[O:21])[CH2:17][CH2:16][CH2:15][N:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1

Komponenten

7

Edukt 4

HCID 51282-IodotolueneHCID 6342AcetonitrileHCID 6422Trifluoroacetic acid2×HCID 784031-Piperidinebutyronitrile

Produkt 1

HCID 9794847[4-(2-Methylphenyl)-4-oxo-1-butyl]piperidine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a 10 mL oven-dried flask was added Mg turnings (97 mg, 4.1 mmol) which was activated by the use of a heat-gun under vacuum. Under inert atmosphere was added a suspension of 2-iodo-toluene (380 mL, 3.0 mmol) in Et2O (3 mL) and the reaction mixture was allowed to reflux for 1 hours. A suspension of 4-piperidin-1-yl-butanenitrile 10 (Dahlbom et. al. Acta. Chem. Scand. 1951, 5, 690-697) (0.305 mg, 2.0 mmol) in CH2Cl2 (3 mL) was added via a syringe and the reaction mixture was stirred at rt overnight. The reaction mixture was quenched by addition of H2SO4 (10 mL, 2 M) and stirred at rt for 12 hours followed by addition of NaOH (12 mL, 2 M). Addition of THF (15 mL) was followed by extraction with ethyl acetate (3×50 mL), and the combined organic phases are washed with brine (10 mL) and NaOH (10 mL, 2 M), and dried (MgSO4) and evaporated to dryness to produce 0.21 g of crude 11. The crude product was subjected to preparative HPLC [eluent: Buffer A: 0.1% TFA; Buffer B: 80% CH3CN+0.1%TFA] to produce an analytically pure sample of compound 11; LC-MS [M+H]+ 245 (cald. 245.2).

Aufarbeitung

  1. customIn a 10 mL oven-dried flask
  2. temperaturea heat-gun under vacuum
  3. additionUnder inert atmosphere was added
  4. temperatureto reflux for 1 hours
  5. additionwas added via a syringe
  6. customThe reaction mixture was quenched by addition of H2SO4 (10 mL, 2 M)
  7. stirringstirred at rt for 12 hours
  8. additionfollowed by addition of NaOH (12 mL, 2 M)
  9. additionAddition of THF (15 mL)
  10. extractionwas followed by extraction with ethyl acetate (3×50 mL)
  11. washthe combined organic phases are washed with brine (10 mL) and NaOH (10 mL, 2 M)
  12. dry with materialdried (MgSO4)
  13. customevaporated to dryness
  14. customto produce 0.21 g of crude 11

Quellen und Nachweise

ORD-Eintrag
ord-a118f632ccae42058a9d1b0a9fa0e2cd
Quelldatensatz
uspto-grants-2009_02
Patentnummer
US07485651B2

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