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

HRID 1622497Notes

Reaction equation

HRID 1622497 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH:11]3[CH2:13][CH2:12]3)[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]3[CH2:12][CH2:13]3)[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 866878524-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine

Product 1

HCID 866878534-(4-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine

Reagents, catalysts & solvents 1

HCID 67553Tetrabutylammonium IodideCatalyst

Procedure

4-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine (3.42 g, 8.06 mmol) was stirred in 6M sodium hydroxide (70 mL, 420 mmol) solution with 1-bromo-2-(2-bromoethoxy)ethane (5.03 mL, 40.3 mmol) and tetrabutylammonium iodide (0.298 g, 0.806 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 Et2O/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 dissolved in CHCl3, loaded onto a silica column, and was purified by flash chromatography eluting with EtOAc/Hex 20% to 40% over 20 column volumes. The fractions containing the desired compound by TLC were combined and concentrated and the resultant dark oil was triturated with Et2O/Hexanes to provide 4-(4-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine (1.62 g, 3.28 mmol, 40.7% yield) as a light orange solid. MS (ES+) m/e: 495.1, 495.8 [M+H]+

Workup

  1. temperaturewas cooled
  2. customthe aqueous was decanted
  3. dissolutionthe remaining sticky solid was dissolved in Et2O/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-b3f1432dd05744a292c863ff222570b1
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

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