Tetrahydrofuran → [2-(4-Fluoro-benzyl)-phenyl]-acetonitrile

HRID 2378497Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2378497
[F:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][C:7]2[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=2[C:9](O)=O)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[BH4-].[Na+].C1COCC1.[CH2:29]([N:31](CC)CC)C.C([N+](CCCC)(CCCC)CCCC)CCC.[C-]#N.[Na+]>C1(C)C=CC=CC=1.O.CC(C)=O.CN(C=O)C>[F:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][C:7]2[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=2[CH2:9][C:29]#[N:31])=[CH:4][CH:3]=1

Komponenten

12

Edukt 7

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 8929Sodium CyanideHCID 16028TetrabutylammoniumHCID 24386Thionyl Chloride2×HCID 4311764Sodium borohydrideHCID 117363592-(4-Fluorobenzyl)benzoic acid

Produkt 1

HCID 11206883[2-(4-Fluoro-benzyl)-phenyl]-acetonitrileAusbeute 94 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 180AcetoneLösungsmittelHCID 962WaterLösungsmittel3×HCID 1140TolueneLösungsmittel2×HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

2-(4-fluoro-benzyl)-benzoic acid is dissolved in toluene (1.5 L/mol) and DMF (1 ml/mol) is added. The reaction mixture is heated up to 40° C. and thionyl chloride (1.1 eq.) is added. During the addition the reaction mixture is further heated up to 50° C. The reaction mixture is stirred at 50° C. during 2.5 hours, then evaporated at 50° C. under vacuum. THF (0.3 L/mol) is added and that solution is dropped into a 2 M NaBH4 solution in THF (1.5 eq.). The temperature rises to reflux (67° C.) and the reaction mixture is stirred at reflux during 2 hours. The reaction mixture is cooled down to room temperature. Acetone (350 ml/mol) is added (temperature rises to 40° C.), the reaction mixture is stirred during 30 minutes, followed by toluene (1 L/mol) and water (1.5 L/mol). The reaction mixture is heated up to 50° C. and the organic layer is evaporated at 50° C. under vacuum. CH2Cl2 (3 L/mol) is added, followed by triethylamine (1.1 eq.). SOCl2 (1.1 eq.) is added dropwise, the temperature rises to reflux. The reaction mixture is stirred during 45 min to room temperature. Water (1 L/mol) is added and the reaction mixture is stirred vigorously during 15 min. The organic layer is washed a second time with water (1 L/mol) and evaporated (40° C., vac.). The product is dissolved in toluene (2.5 L/mol), tetrabutylammonium hydrogenosulfate (phase-transfer catalyst) (0.1 eq.) is added at 70° C. and sodium cyanide 6 M (1.6 eq.) is added at 70° C. under vigorous stirring. The reaction mixture is then heated up to reflux and stirred during 3 hours. After cooling down to room temperature, water (0.5 L/mol) is added and the reaction mixture is stirred during 30 minutes. After washing a second time with water (0.5 L/mol), drying on magnesium sulphate and evaporating the solvent, [2-(4-fluoro-benzyl)-phenyl]-acetonitrile is obtained. Active yield: 94%. N.B. The product can be purified with e.g. thin-film distillation.

Aufarbeitung

  1. additionDuring the addition the reaction mixture
  2. temperatureis further heated up to 50° C
  3. customevaporated at 50° C. under vacuum
  4. additionTHF (0.3 L/mol) is added
  5. temperatureto reflux (67° C.)
  6. stirringthe reaction mixture is stirred
  7. temperatureat reflux during 2 hours
  8. temperatureThe reaction mixture is cooled down to room temperature
  9. stirringthe reaction mixture is stirred during 30 minutes
  10. temperatureThe reaction mixture is heated up to 50° C.
  11. customthe organic layer is evaporated at 50° C. under vacuum
  12. additionCH2Cl2 (3 L/mol) is added
  13. temperatureto reflux
  14. stirringThe reaction mixture is stirred during 45 min to room temperature
  15. stirringthe reaction mixture is stirred vigorously during 15 min
  16. washThe organic layer is washed a second time with water (1 L/mol)
  17. customevaporated (40° C., vac.)
  18. dissolutionThe product is dissolved in toluene (2.5 L/mol)
  19. temperatureThe reaction mixture is then heated up
  20. temperatureto reflux
  21. stirringstirred during 3 hours
  22. temperatureAfter cooling down to room temperature
  23. stirringthe reaction mixture is stirred during 30 minutes
  24. washAfter washing a second time with water (0.5 L/mol)
  25. customdrying on magnesium sulphate
  26. customevaporating the solvent

Quellen und Nachweise

ORD-Eintrag
ord-b748c091f7f14e0d8f1d673db6136c6f
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07470809B2

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