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

HRID 1622462Notes

Reaction equation

HRID 1622462 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:13]=3[CH3:22])[C:6]=2[CH:5]=[C:4]([NH2:23])[CH:3]=1.[OH-].[Na+].Br[CH2:27][CH2:28][O:29][CH2:30][CH2:31]Br>[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Br:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:19])([F:21])[F:20])[C:13]=3[CH3:22])[C:6]=2[CH:5]=[C:4]([N:23]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21521Bis(2-bromoethyl) etherHCID 866878244-bromo-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine

Product 1

HCID 866878254-(4-bromo-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholineYield 18.9%

Reagents, catalysts & solvents 1

HCID 67553Tetrabutylammonium IodideCatalyst

Conditions

Temperature
110 °C

Procedure

Into a 100 ml round bottomed flask with 4-bromo-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine (2.28 g, 5.93 mmol), tetrabutylammonium iodide (0.110 g, 0.297 mmol) was added 6N sodium hydroxide (14.84 ml, 89 mmol) and 1-bromo-2-(2-bromoethoxy)ethane (1.480 ml, 11.87 mmol). The reaction was heated to 110° C. for 2 h, cooled to room temperature and the mixture was extracted with EtOAc. The combined organic phase was washed with Brine (20 mL) and concentrated. The residue was purified on a silica gel cartridge and eluted with a gradient of 0% ethyl acetate/hexanes to 80% over 10 column volumes. The appropriate fractions were collected and evaporated to yield 4-(4-bromo-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine (508 mg, 1.118 mmol, 18.84% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.40 (s, 3H) 3.00-3.09 (m, 4H) 3.76-3.81 (m, 4H) 5.26 (s, 2H) 6.54 (d, J=2.02 Hz, 1H) 6.85 (d, J=7.58 Hz, 1H) 7.13-7.21 (m, 2H) 7.57 (d, J=7.83 Hz, 1H) 7.68 (s, 1H); LC/MS: MS (ES+) m/e 455 [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. extractionthe mixture was extracted with EtOAc
  3. washThe combined organic phase was washed with Brine (20 mL)
  4. concentrationconcentrated
  5. customThe residue was purified on a silica gel cartridge
  6. washeluted with a gradient of 0% ethyl acetate/hexanes to 80% over 10 column volumes
  7. customThe appropriate fractions were collected
  8. customevaporated

Sources & evidence

ORD record
ord-e4beef904f4042d582798df18eda81d1
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

Loading…