Hydrochloric Acid → 4-bromo-1-(3-chloro-2-methylbenzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-6-amine

HRID 1622486Notes

Reaction equation

HRID 1622486 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[C:8]([C:11]([F:14])([F:13])[F:12])[N:7]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[C:17]=3[CH3:23])[C:6]=2[CH:5]=[C:4]([N+:24]([O-])=O)[CH:3]=1.O.O.[Sn](Cl)Cl.Cl>CO>[Br:1][C:2]1[C:10]2[N:9]=[C:8]([C:11]([F:14])([F:13])[F:12])[N:7]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[C:17]=3[CH3:23])[C:6]=2[CH:5]=[C:4]([NH2:24])[CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 61436Stannous chloride dihydrateHCID 866878434-bromo-1-(3-chloro-2-methylbenzyl)-6-nitro-2-(trifluoromethyl)-1H-benzo[d]imidazole

Product 1

HCID 866878444-bromo-1-(3-chloro-2-methylbenzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-6-amineYield 76.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a 100 mL round-bottom flask containing MeOH (25 mL) was added 4-bromo-1-(3-chloro-2-methylbenzyl)-6-nitro-2-(trifluoromethyl)-1H-benzo[d]imidazole (5.3 g, 11.81 mmol), tin(II) chloride dihydrate (8.00 g, 35.4 mmol) and hydrochloric acid (4.92 mL, 59.1 mmol). The resultant suspension was heated to 50° C. and monitored by LC/MS. By LC/MS the reaction was complete in 30 minutes. After the reaction had cooled to room temperature, the majority of the MeOH was removed in-vacuo and 6N aqueous sodium hydroxide solution was added to adjust the pH to pH>10 and the mixture was extracted with ethyl acetate (50 mL). The organic layer was washed with H2O and brine then dried over MgSO4 and filtered. The solvent was removed in vacuo and the crude solid was purified by chromatography on silica gel eluted with chloroform/(solution of 2N ammonia in methanol) [95:5]. The fractions corresponding to product were combined, then concentrated in vacuo to provide 4-bromo-1-(3-chloro-2-methylbenzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-6-amine (3.78 g, 9.03 mmol, 76% yield) as a light yellow solid. MS (ES+) m/e: 419.0, 420.0 [M+H]+; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.34 (d, J=8.08 Hz, 1H) 6.95-7.05 (m, 2H) 6.21-6.32 (m, 2H) 5.39 (s, 2H) 3.84 (s, 2H) 2.49 (s, 3H)

Workup

  1. customthe majority of the MeOH was removed in-vacuo and 6N aqueous sodium hydroxide solution
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate (50 mL)
  4. washThe organic layer was washed with H2O and brine
  5. dry with materialthen dried over MgSO4
  6. filtrationfiltered
  7. customThe solvent was removed in vacuo
  8. customthe crude solid was purified by chromatography on silica gel
  9. washeluted with chloroform/(solution of 2N ammonia in methanol) [95:5]
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-477b7f92cabe48ca922f67ea5f2b090a
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

Loading…