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

HRID 1622465Notes

Reaction equation

HRID 1622465 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]([Cl:18])[C:13]=3[CH3:19])[C:6]=2[CH:5]=[C:4]([NH2:20])[CH:3]=1.[OH-].[Na+].Br[CH2:24][CH2:25][O:26][CH2:27][CH2:28]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]([Cl:18])[C:13]=3[CH3:19])[C:6]=2[CH:5]=[C:4]([N:20]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21521Bis(2-bromoethyl) etherHCID 866878274-bromo-1-(3-chloro-2-methylbenzyl)-1H-benzo[d]imidazol-6-amine

Product 1

HCID 866878284-(4-bromo-1-(3-chloro-2-methylbenzyl)-1H-benzo[d]imidazol-6-yl)morpholineYield 17.3%

Reagents, catalysts & solvents 1

HCID 67553Tetrabutylammonium IodideCatalyst

Conditions

Temperature
110 °C

Procedure

Into a 100 ml round bottomed flask with 4-bromo-1-(3-chloro-2-methylbenzyl)-1H-benzo[d]imidazol-6-amine (2.33 g, 6.64 mmol), tetrabutylammonium iodide (0.123 g, 0.332 mmol) was added 6N sodium hydroxide (16.61 ml, 100 mmol) and 1-bromo-2-(2-bromoethoxy)ethane (1.657 ml, 13.29 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 by reversed phase HPLC and was eluted with a gradient of acetonitrile (0.1% TFA) and water (0.1% TFA v/v) (30-65%) over 12 minutes. The appropriate fractions were collected and evaporated to yield 4-(4-bromo-1-(3-chloro-2-methylbenzyl)-1H-benzo[d]imidazol-6-yl)morpholine (483 mg, 1.148 mmol, 17.28% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.37 (s, 3H) 3.14-3.22 (m, 4H) 3.84-3.93 (m, 4H) 5.48 (s, 2H) 6.71 (d, J=2.02 Hz, 1H) 6.91 (d, J=7.58 Hz, 1H) 7.16 (t, J=7.83 Hz, 1H) 7.34 (d, J=2.02 Hz, 1H) 7.44 (d, J=7.58 Hz, 1H) 8.84 (br. s., 1H); LC/MS: MS (ES+) m/e 421 [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 by reversed phase HPLC
  6. washwas eluted with a gradient of acetonitrile (0.1% TFA) and water (0.1% TFA v/v) (30-65%) over 12 minutes
  7. customThe appropriate fractions were collected
  8. customevaporated

Sources & evidence

ORD record
ord-749cb160699649d291500bdb2f457c4f
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

Loading…