1,1'-Carbonyldiimidazole → Ethyl 3-(2-fluoro-5-iodophenyl)-3-oxopropanoate

HRID 411198Notes

Reaction equation

HRID 411198 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[F:13][C:14]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:15]=1[C:16]([OH:18])=O.C1CCN2C(=NCCC2)CC1.C[Si]([CH:39](C([O-])=O)[C:40]([O:42][CH2:43][CH3:44])=[O:41])(C)C>C1COCC1.C(#N)C>[F:13][C:14]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:15]=1[C:16](=[O:18])[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27789252-Fluoro-5-iodobenzoic acidHCID 22397230Ethyl trimethylsilylmalonate

Product 1

HCID 22397214Ethyl 3-(2-fluoro-5-iodophenyl)-3-oxopropanoateYield 71.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

Employing the method utilized by Wang (Wang, X., Monte, W. T., Napier, J. J., Ghannam, A. Tetrahedron. Lett. 1994, 35, 9323), 1,1′-carbonyldiimidazole (1.82 g) in THF (20 mL) at 0° C. is treated with 2-fluoro-5-iodobenzoic acid (2.66 g) prepared according to literature procedures (Blackburn, B. K., Lee, A., Baier, M., Kohl, B., Olivero, A. G., Matamoros, R., Robarge, K. D., McDowell, R. S. J. Med Chem. 1997, 40, 717-729.) in portions over a 10 minute period. The mixture is stirred for 1 h and then allowed to warm to room temperature for an additional 1 h. The solution is then added dropwise into an enolate solution of ethyl trimethylsilymalonate at 5° C. prepared by the addition of DBU (3.35 g) to a solution of ethyl trimethylsilylmalonate (2.25 g) in acetonitrile (20 mL) at 5° C. with stirring for 45 minutes. The reaction mixture is allowed to warm to room temperature and stirred overnight. The orange solution is quenched with 100 mL of aqueous 10% citric acid solution and extracted with ethyl acetate. The organic extract is washed with aqueous 10% sodium bicarbonate solution and water, dried (Na2SO4), and concentrated in vacuo to give 2.4 g of the title compound as a yellow liquid. Physical characteristics: tlc Rf=0.66 (silica gel G; 20% EtOAc/hexane, visualize with I2).

Workup

  1. customprepared
  2. stirringwith stirring for 45 minutes
  3. temperatureto warm to room temperature
  4. stirringstirred overnight
  5. customThe orange solution is quenched with 100 mL of aqueous 10% citric acid solution
  6. extractionextracted with ethyl acetate
  7. extractionThe organic extract
  8. washis washed with aqueous 10% sodium bicarbonate solution and water
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-248ab757536c4a48be17a03b98964705
Source dataset
uspto-grants-2003_05
Patent number
US06559145B2

Reaction notes

Loading…