1-Bromo-4-fluorobenzene → 2-(4-Fluorophenyl)-5-[(tetra-hydro-2-pyranyloxy)methyl]pyridine

HRID 372923

Reaktionsgleichung

Reaktionsgleichung von HRID 372923
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1.Cl[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)=[CH:13][N:12]=1>CC(P(C1C=CC=CC=1)C1C=CC=CC=1)C.C1C=CC(PC2C=CC=CC=2)=CC=1.[Cl-].[Ni].O1CCCC1>[F:9][C:6]1[CH:7]=[CH:8][C:3]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][O:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)=[CH:13][N:12]=2)=[CH:4][CH:5]=1

Komponenten

6

Edukt 3

HCID 99931-Bromo-4-fluorobenzeneHCID 5462224MagnesiumHCID 221273782-Chloro-5-{[(oxan-2-yl)oxy]methyl}pyridine

Produkt 1

HCID 198125972-(4-Fluorophenyl)-5-[(tetra-hydro-2-pyranyloxy)methyl]pyridineAusbeute 77,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 21654969Diphenylphosphane;diphenyl(propan-2-yl)phosphane;nickel;chlorideKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
3 °C

Versuchsvorschrift

A grignard reagent solution prepared from 1.53 g of magnesium, 10.5 g of 1-bromo-4-fluorobenzene and 70 ml of tetrahydrofuran was added dropwise at 3°-7° C. within 45 minutes to a mixture of 16.9 g of crude 2-chloro-5-[(tetrahydro-2-pyranyloxy)methyl]pyridine, 60 ml of tetrahydrofuran and 0.62 g of 1,3-bis(diphenylphosphino)-propanenickel-(II) chloride. The dark reaction mixture was stirred at 3° C. for a further 1 hr. and at room temperature for 2 hrs. and then extracted with 200 ml of diethyl ether and 120 ml of 0.5N ammonium chloride solution. The organic phase was washed neutral with water, dried over sodium sulphate, filtered and concentrated. Chromatographic purification of the residue on 230 g of silica gel with hexane/ethyl acetate (vol. 9:1) yielded 13.4 g of 2-(4-fluorophenyl)-5-[(tetra-hydro-2-pyranyloxy)methyl]pyridine as a yellowish oil.

Aufarbeitung

  1. customThe dark reaction mixture
  2. waitand at room temperature for 2 hrs
  3. extractionand then extracted with 200 ml of diethyl ether and 120 ml of 0.5N ammonium chloride solution
  4. washThe organic phase was washed neutral with water
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customChromatographic purification of the residue on 230 g of silica gel with hexane/ethyl acetate (vol. 9:1)

Quellen und Nachweise

ORD-Eintrag
ord-01403faf49f2441c9fe1f5aa642fa0aa
Quelldatensatz
uspto-grants-1992_11
Patentnummer
US05160661

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