3,4-dihydro-2H-pyran → 5-bromo-4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole

HRID 475228Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 475228
[Br:1][C:2]1[CH:10]=[CH:9][C:5]2[NH:6][CH:7]=[N:8][C:4]=2[C:3]=1[F:11].[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1COCC1>[Br:1][C:2]1[CH:10]=[CH:9][C:5]2[N:6]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17][O:12]3)[CH:7]=[N:8][C:4]=2[C:3]=1[F:11]

Komponenten

5

Edukt 3

HCID 80803,4-dihydro-2H-pyranHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 594744775-bromo-4-fluoro-1H-1,3-benzodiazole

Produkt 1

HCID 866947315-bromo-4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazoleAusbeute 78,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 144 (24 g, 0.111 mol) in dry THF (720 mL) was added 3,4-dihydro-2H-pyran (28.1 g, 0.334 mol) and camphorsulfonic acid (2.6 g, 0.011 mol) then heated to reflux for 16 h. The resulting mixture was concentrated and the residue purified by SiO2 chromatography eluting with 20% EtOAc/petroleum ether to afford 26 g (78%) of 5-bromo-4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole (146) as pale yellow oil: 1H-NMR (400 MHz, RT, DMSO-d6): δ 1.57-1.63 (m, 2H), 1.70-1.74 (m, 1H), 1.91-2.04 (m, 2H), 2.15-2.19 (m, 1H), 3.73-3.77 (m, 1H), 3.96-4.03 (m, 1H), 5.68-5.71 (dd, 1H), 7.50-7.53 (d, 2H), and 8.51 (s, 1H); MS (ESI): m/z=301.0 [M+1]+.

Aufarbeitung

  1. temperaturethen heated
  2. temperatureto reflux for 16 h
  3. concentrationThe resulting mixture was concentrated
  4. customthe residue purified by SiO2 chromatography
  5. washeluting with 20% EtOAc/petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-43415d75bb2a4056a0712e3cc8c77ed2
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08637537B2

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