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

HRID 475228Notes

Reaction equation

HRID 475228 reaction equation
[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]

Participants

5

Reactant 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

Product 1

HCID 866947315-bromo-4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazoleYield 78.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-43415d75bb2a4056a0712e3cc8c77ed2
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

Loading…