Sodium Hydroxide → 4-(4-bromo-2-isopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine

HRID 1622492Notes

Reaction equation

HRID 1622492 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH:11]([CH3:13])[CH3:12])[N:7]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[C:16]=3[CH3:25])[C:6]=2[CH:5]=[C:4]([NH2:26])[CH:3]=1.[OH-].[Na+].Br[CH2:30][CH2:31][O:32][CH2:33][CH2:34]Br>[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH:11]([CH3:13])[CH3:12])[N:7]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:24])[F:23])[C:16]=3[CH3:25])[C:6]=2[CH:5]=[C:4]([N:26]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21521Bis(2-bromoethyl) etherHCID 866878484-bromo-2-isopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine

Product 1

HCID 866878494-(4-bromo-2-isopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine

Reagents, catalysts & solvents 1

HCID 67553Tetrabutylammonium IodideCatalyst

Procedure

The product from previous reaction 4-bromo-2-isopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine (4.7 g, 11.03 mmol) was stirred in 6M sodium hydroxide (100 mL, 600 mmol) solution with 1-bromo-2-(2-bromoethoxy)ethane (6.87 mL, 55.1 mmol) and tetrabutylammonium iodide (0.407 g, 1.103 mmol) at 110° C. After stirring for 2.5 hr the mixture was cooled and the aqueous was decanted and the remaining sticky solid was dissolved in EtOAc. The organic was washed with H2O and brine and dried over MgSO4 and concentrated to leave a thick dark residue containing the desired product. The desired product was purified by flash chromatography on a silica column eluting with EtOAc/Hex 15% to 40% over 20 column volumes. The fractions containing the desired compound by TLC were combined and concentrated to provide 4-(4-bromo-2-isopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine (2.75 g, 4.99 mmol, 45.2% yield) as a light orange solid. MS (ES+) m/e: 495.1, 496.1 [M+H]+

Workup

  1. temperaturewas cooled
  2. customthe aqueous was decanted
  3. dissolutionthe remaining sticky solid was dissolved in EtOAc
  4. washThe organic was washed with H2O and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto leave a thick dark residue

Sources & evidence

ORD record
ord-7e8b293d27934b6583eb9b07201fa57b
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

Loading…