Carbon Dioxide → 5-(3-Bromo-5-formyl-furan-2-yl)-3-(4-chloro-phenyl)-[1,2,4]-oxadiazole

HRID 1823858Notes

Reaction equation

HRID 1823858 reaction equation
[Br:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7]1[O:11][N:10]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[N:8]=1.C([N-]C(C)C)(C)C.[Li+].CN([CH:30]=[O:31])C.C(=O)=O>O1CCCC1>[Br:1][C:2]1[CH:6]=[C:5]([CH:30]=[O:31])[O:4][C:3]=1[C:7]1[O:11][N:10]=[C:9]([C:12]2[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=2)[N:8]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 6228DimethylformamideHCID 2724682Lithium diisopropylamideHCID 98584885-(3-Bromo-furan-2-yl)-3-(4-chloro-phenyl)-[1,2,4]oxadiazole

Product 1

HCID 221478875-(3-Bromo-5-formyl-furan-2-yl)-3-(4-chloro-phenyl)-[1,2,4]-oxadiazoleYield 60.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5-(3-bromo-furan-2-yl)-3-(4-chloro-phenyl)-[1,2,4]-oxadiazole (599 mg, 1.84 mmol) in tetrahydrofuran (10 mL) was added under argon over 20 min to a stirred solution of 1.5 M lithium diisopropylamide (1.3 mL, 1.95 mmol) and tetrahydrofuran (10 mL) in a dry ice/acetone bath, and it was stirred for 1 h. To the solution was then added dry DMF (1.5 mL, 19.4 mmol) dropwise and the solution was stirred for 30 min. The dry ice bath was replaced by an ice bath and the solution was stirred for 20 min. The ice bath was removed and the solution was quenched with methanol (10 mL) and then saturated sodium bicarbonate (3 mL). To the solution was added 1 N hydrochloric acid until the solution reach pH 3. The solution was extracted with dichloromethane (2×100 mL). The extracts were dried over sodium sulfate, filtered, and concentrated. The product was purified twice by column chromatography (dichloromethane) to yield 393 mg (60%) of the title compound as a light yellow solid. 1H NMR (DMSO-d6): 9.79 (s, 1H), 8.11 (dd, J=8.52, 2.13 Hz, 2H), 8.05 (s, 1H), 7.70 (dd, J=8.24, 2.06 Hz, 2H).

Workup

  1. stirringthe solution was stirred for 30 min
  2. stirringthe solution was stirred for 20 min
  3. customThe ice bath was removed
  4. customthe solution was quenched with methanol (10 mL)
  5. additionTo the solution was added 1 N hydrochloric acid until the solution
  6. extractionThe solution was extracted with dichloromethane (2×100 mL)
  7. dry with materialThe extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe product was purified twice by column chromatography (dichloromethane)

Sources & evidence

ORD record
ord-fe4e3868f41b44269d76cda7de2a393d
Source dataset
uspto-grants-2006_05
Patent number
US07041685B2

Reaction notes

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