Tetrafluoroboric acid → 2-n-Butyl-1-{(2-chlorophenyl)methyl}-4-fluoro-5-carboethoxyimidazole

HRID 2081854Notes

Reaction equation

HRID 2081854 reaction equation
[F:1][B-](F)(F)F.[H+].[CH2:7]([C:11]1[N:12]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:29])[C:13]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:14](N)[N:15]=1)[CH2:8][CH2:9][CH3:10].N([O-])=O.[Na+]>O>[CH2:7]([C:11]1[N:12]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:29])[C:13]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:14]([F:1])[N:15]=1)[CH2:8][CH2:9][CH3:10]

Participants

5

Reactant 3

HCID 28118Tetrafluoroboric acidHCID 19936798HCID 19936798, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 199369122-n-Butyl-1-{(2-chlorophenyl)methyl}-4-fluoro-5-carboethoxyimidazole

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

The 4-amino product was fluorinated using the procedure of K. L. Kirk and L. J. Cohen, JACS, 95 (14), 4619 (1973). Fluoroboric acid (48%, 150 mL) was added to 2-n-butyl-1-{(2-chlorophenyl)methyl}-4-amino-5-carboethoxyimidazole (10.75 g, 0.032 mol) in a quartz flask. The resulting solid mass was sonicated and stirred vigorously to form a suspension. This suspension was cooled to 0° C. and then sodium nitrite (2.80 g, 0.0406 mol) in 5 mL of water was added slowly. The ice bath was removed and then the reaction mixture was irradiated for 20 hours with a 450-watt mercury vapor lamp placed in a quartz immersion well, cooled by circulating 1 water. The reaction mixture was cooled to -20° C. and the pH was adjusted to 6.4 with 50% aqueous sodium hydroxide. The product was extracted into ethyl acetate (3x) and the combined extracts were washed with water and saturated sodium chloride solution. The organic extract was dried with anhydrous sodium sulfate and concentrated to give 8.43 g of a crude product, which was chromatographed on silica gel eluting with chloroform to give 4.31 g of 2-n-butyl-1-{(2-chlorophenyl)methyl}-4-fluoro-5-carboethoxyimidazole.

Workup

  1. customThe resulting solid mass was sonicated
  2. customto form a suspension
  3. customThe ice bath was removed
  4. customthe reaction mixture was irradiated for 20 hours with a 450-watt mercury vapor lamp
  5. temperaturecooled
  6. temperatureThe reaction mixture was cooled to -20° C.
  7. extractionThe product was extracted into ethyl acetate (3x)
  8. washthe combined extracts were washed with water and saturated sodium chloride solution
  9. extractionThe organic extract
  10. dry with materialwas dried with anhydrous sodium sulfate
  11. concentrationconcentrated
  12. customto give 8.43 g of a crude product, which
  13. customwas chromatographed on silica gel eluting with chloroform

Sources & evidence

ORD record
ord-da7c4995a93449189156fb29bd13b2ac
Source dataset
uspto-grants-1993_02
Patent number
US05185351

Reaction notes

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