Ethyl Acetate → 7-Fluoro-1H-benzo[d]imidazole-5-carboxylic acid

HRID 2404252Notes

Reaction equation

HRID 2404252 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:11])[C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:10]=1.[C:12](=O)([O-:14])[O-:13].[Na+].[Na+].C(OCC)(=O)C>O1CCOCC1.O.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo]>[F:11][C:4]1[C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:10]=[C:2]([C:12]([OH:14])=[O:13])[CH:3]=1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 669205005-Bromo-7-fluoro-1H-benzo[D]imidazole

Product 1

HCID 671513687-Fluoro-1H-benzo[d]imidazole-5-carboxylic acidYield 63%

Reagents, catalysts & solvents 3

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
155 °C

Procedure

To a 2.5-5 mL microwave tube, was added 6-bromo-4-fluoro-1H-benzo[d]imidazole (160 mg, 0.744 mmol) suspended in de-gassed 1,4 dioxane (1.5 mL). To this was added trans-di(u-acetato)bis[o-(di-o-tolylphino)benzyl]di-palladium (II) (26 mg, 0.043 mmol) and molybdenum hexacarbonyl (100 mg, 0.38 mmol), along with sodium carbonate (237 mg, 2.23 mmol) dissolved in de-gassed water (2 mL). The mixture was stirred for 20 seconds and then heated at 155° C. in the microwave for 10 minutes, keeping the pressure under 16 bar. The vessel was vented before handling and left to stand overnight at room temperature. Water (2 mL) and ethyl acetate (3 mL) were added to the reaction, and then the mixture was filtered through Celite®. The filtrate was partitioned with ethyl acetate and separated. The aqueous fraction was washed with ethyl acetate once more and the combined organic layers were set aside. Another portion of water (5 mL) was added to the aqueous layer and acidified with 0.5 M HCl to pH 3; a brown precipitate was formed. The mixture was allowed to stand in the refrigerator at 4° C. for 1 hour. The mixture was filtered and washed with water to give 4-fluoro-1H-benzo[d]imidazole-6-carboxylic acid as a grey solid, (63% yield). 1H NMR (500 MHz, DMSO-d6) □ ppm 1299 (br. s., 1H) 8.47 (s, 1H) 8.02 (s, 1H) 7.52 (d, J=11.71 Hz, 1H).

Workup

  1. waitleft
  2. waitto stand overnight at room temperature
  3. filtrationthe mixture was filtered through Celite®
  4. customThe filtrate was partitioned with ethyl acetate
  5. customseparated
  6. washThe aqueous fraction was washed with ethyl acetate once more
  7. additionAnother portion of water (5 mL) was added to the aqueous layer
  8. customa brown precipitate was formed
  9. waitto stand in the refrigerator at 4° C. for 1 hour
  10. filtrationThe mixture was filtered
  11. washwashed with water

Sources & evidence

ORD record
ord-bc582806aa194ff6bfdc72533421f522
Source dataset
uspto-grants-2014_08
Patent number
US08802690B2

Reaction notes

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