HCID 19430487, compound → HCID 19430452, compound

HRID 1078036Notes

Reaction equation

HRID 1078036 reaction equation
[F:1][C:2]1[CH:20]=[C:19]([I:21])[CH:18]=[CH:17][C:3]=1[CH2:4][N:5]1[C:9]([CH:10]=[O:11])=[C:8]([CH2:12][CH3:13])[N:7]=[C:6]1[CH2:14][CH2:15][CH3:16].[CH3:22][Mg]Br>C1COCC1.[O-2].[Mn+4].[O-2]>[F:1][C:2]1[CH:20]=[C:19]([I:21])[CH:18]=[CH:17][C:3]=1[CH2:4][N:5]1[C:9]([C:10](=[O:11])[CH3:22])=[C:8]([CH2:12][CH3:13])[N:7]=[C:6]1[CH2:14][CH2:15][CH3:16]

Participants

5

Reactant 2

HCID 19430487HCID 19430487, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 19430452HCID 19430452, compoundYield 27.5%

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(2-fluoro-4-iodobenzyl)-4-ethyl-2-propyl-1H-imidazole-5-carboxaldehyde (16.52 g, 41.3 mmol) in THF (100 mL) was added methylmagnesium bromide (44.0 mL of 1.4/M in toluene/THF, 61.6 mmol) over 30 minutes. The reaction mixture was stirred at room temperature for 1.5 h. It was then quenched with 100 mL of 1N aqueous HCl. The mixture was extracted with CH2Cl2, the organic solution was washed with H2O and brine, dried over MgSO4, and concentrated to a yellow oil (16.87 g). The yellow oil was dissolved in 400 mL of CH2Cl2, and Manganese(IV) oxide (70.50 g, 811 mmol) was added. The mixture was refluxed under N2 overnight. The mixture was cooled. It was then filtered through celite and washed with CH2Cl2. The CH2Cl2 solution was concentrated and chromatographed on silica gel with 50% EtOAc/hexane and 10% MeOH/CH2Cl2 to give 4.70 g of the desired product and 6.87 g of the alcohol. MS m/e 415.0, [M+H]+ ; 1H NMR (300 MHz, CDCl3): δ 0.98 (t, 3H, CH3), 1.35 (t, 3H, CH3), 1.68 (m, 2H, CH2), 2.42 (s, 3H, CH3) 2.58 (m, 2H, CH2), 2.92 (q, 2H, CH2), 5.45 (s, 2H, CH2Ar), 6.28 (t, 1H, ArH), 7.35 (d, 1H, ArH), 7.42 (d, 1H, ArH). ##STR63##

Workup

  1. customIt was then quenched with 100 mL of 1N aqueous HCl
  2. extractionThe mixture was extracted with CH2Cl2
  3. washthe organic solution was washed with H2O and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to a yellow oil (16.87 g)
  6. dissolutionThe yellow oil was dissolved in 400 mL of CH2Cl2
  7. temperatureThe mixture was refluxed under N2 overnight
  8. temperatureThe mixture was cooled
  9. filtrationIt was then filtered through celite
  10. washwashed with CH2Cl2
  11. concentrationThe CH2Cl2 solution was concentrated
  12. customchromatographed on silica gel with 50% EtOAc/hexane and 10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-54e5b0ac221a4016ad4e865a4b7177fc
Source dataset
uspto-grants-1996_08
Patent number
US05545651

Reaction notes

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