Hydrogen Bromide → HCID 22482479, compound

HRID 2182100Notes

Reaction equation

HRID 2182100 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([O:14]C)[C:8]=2[N:7]=[C:6]1[C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=1[F:23].Br>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.C(O)(=O)C>[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([OH:14])[C:8]=2[N:7]=[C:6]1[C:16]1[C:17]([F:23])=[CH:18][CH:19]=[CH:20][C:21]=1[F:22]

Participants

5

Reactant 2

HCID 260Hydrogen BromideHCID 492672HCID 492672, compound

Product 1

HCID 22482479HCID 22482479, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 5974Hexadecyltrimethylammonium BromideCatalystHCID 176Acetic AcidSolvent

Procedure

To 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-methoxylbenzimidazole (Example 46) (0.30 g, 0.78 mmol) and hexadecyltrimethylammonium bromide (0.30 g) dissolved in acetic acid (9.0 mL) was added HBr (1.0 mL). After refluxing for 7 h, the reaction was concentrated. The residue was then diluted with EtOAc, and washed with NaHCO3 (sat. aq) and NaCl (sat. aq). The combined washing were dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash chromatography eluting with 2% methanol/CH2Cl2 and recrystallization from diethylether, yielding 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxyl-benzimidazole (0.25 g, 0.67 mmol, 86% yield). M.p. 257-259° C. 1H NMR (200 MHz, CD2Cl2): δ 7.57 (m, 1H, H4′), 7.25 (m, 1H, H4″), 7.17 (dd, J=7.9, 8.3 Hz, 1H, H6), 7.12 (m, 2H, H3′,5′), 6.99 (d, J=8.3 Hz, 1H, H7), 6.82 (m, 2H, H3″,5″), 6.73 (dd, J=7.9, 1.0 Hz, H5), 5.35 (s, 2H, CH2PhF2).

Workup

  1. temperatureAfter refluxing for 7 h
  2. concentrationthe reaction was concentrated
  3. additionThe residue was then diluted with EtOAc
  4. washwashed with NaHCO3 (sat. aq) and NaCl (sat. aq)
  5. washThe combined washing
  6. dry with materialwere dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography
  10. washeluting with 2% methanol/CH2Cl2 and recrystallization from diethylether

Sources & evidence

ORD record
ord-dfde1f04e1aa4b42a1a7215a632e6ade
Source dataset
uspto-grants-2005_05
Patent number
US06894068B2

Reaction notes

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