Formic Acid → 2-[7-(trifluoromethyl)-1H-benzimidazol-1-yl]ethanol

HRID 1991201Notes

Reaction equation

HRID 1991201 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[C:3]=1[NH:12][CH2:13][CH2:14][OH:15].[CH:16](O)=O>>[F:9][C:8]([F:10])([F:11])[C:4]1[C:3]2[N:12]([CH2:13][CH2:14][OH:15])[CH:16]=[N:1][C:2]=2[CH:7]=[CH:6][CH:5]=1

Participants

3

Reactant 2

HCID 284Formic AcidHCID 111953562-{[2-Amino-6-(trifluoromethyl)phenyl]amino}ethanol

Product 1

HCID 112416902-[7-(trifluoromethyl)-1H-benzimidazol-1-yl]ethanolYield 55%

Procedure

A solution of 2-{[2-amino-6-(trifluoromethyl)phenyl]amino}ethanol (0.57 g) in formic acid (20 mL) was heated at reflux for 20 min. The excess of formic acid was removed in vacuo; the residue was dissolved in a 2 M hydrochloric acid, and heated at reflux for 10 min. The solution was concentrated in vacuum and the residue was co-evaporated with acetonitrile and ethanol. The residue was treated with a saturated solution of sodium bicarbonate and extracted twice with ethyl acetate. The organic phase was washed with brine, dried over magnesium sulfate and concentrated. The crude product was purified by column chromatography on silica using ethyl acetate as an eluent affording 2-[7-(trifluoromethyl)-1H-benzimidazol-1-yl]ethanol, 0.36 g (55% yield) as a white solid. MS (ESI) m/z 231 [M+H]. 1H NMR (400 MHz, DMSO-D6) δ ppm 3.74-3.70 (m, 2H), 4.37 (t, J=5.3 Hz, 2H), 5.06 (t, J=4.8 Hz, 1H), 7.39 (t, J=7.8 Hz, 1H), 7.67 (d, J=7.8 Hz, 1H), 8.01 (d, J=8.1 Hz, 1H), 8.33 (s, 1H).

Workup

  1. temperatureat reflux for 20 min
  2. customThe excess of formic acid was removed in vacuo
  3. dissolutionthe residue was dissolved in a 2 M hydrochloric acid
  4. temperatureheated
  5. temperatureat reflux for 10 min
  6. concentrationThe solution was concentrated in vacuum
  7. additionThe residue was treated with a saturated solution of sodium bicarbonate
  8. extractionextracted twice with ethyl acetate
  9. washThe organic phase was washed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated
  12. customThe crude product was purified by column chromatography on silica

Sources & evidence

ORD record
ord-1b5e1c48f0a340bd974c758bbd1a1171
Source dataset
uspto-grants-2010_01
Patent number
US07645784B2

Reaction notes

Loading…