Chlorotrimethylsilane → Ethyl 3-(2-fluoro-5-iodophenyl)-3-oxopropanoate

HRID 1067260Notes

Reaction equation

HRID 1067260 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([I:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl[Si](C)(C)C.[C:29]([O:35][CH2:36][CH3:37])(=[O:34])[CH2:30]C([O-])=O.[K+].C1CCN2C(=NCCC2)CC1>C1COCC1.C(#N)C>[F:1][C:2]1[CH:10]=[CH:9][C:8]([I:11])=[CH:7][C:3]=1[C:4](=[O:6])[CH2:30][C:29]([O:35][CH2:36][CH3:37])=[O:34]

Participants

8

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27789252-Fluoro-5-iodobenzoic acidHCID 3446434Potassium ethyl malonate

Product 1

HCID 22397214Ethyl 3-(2-fluoro-5-iodophenyl)-3-oxopropanoateYield 75.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5.32 g of 2-fluoro-5-iodobenzoic acid from Preparation No. 7 in 20 mL of THF, under argon, is added 3.9 g of carbonyldiimidazole. In a separate flask, 2.8 mL of chlorotrimethylsilane is added to a mixture of 3.74 g of potassium ethyl malonate in 20 mL of acetonitrile. The mixture is stirred under argon for 18 h, then cooled to 0° C. for the dropwise addition of 6.6 mL of DBU. The mixture is stirred for 3 h at 0° C., then the solution of acyl imidazolide prepared above is added via cannula. After 2 hours, the mixture is partitioned between ether and excess dilute HCl, and the organic phase is washed with dilute HCl and brine and dried (MgSO4). Removal of the solvent under reduced pressure left a colorless oil, which is flash chromatographed on silica using 10% ethyl acetate in hexane to provide 5.07 g of the title compound as dense pinkish prisms.

Workup

  1. stirringThe mixture is stirred for 3 h at 0° C.
  2. additionabove is added via cannula
  3. waitAfter 2 hours
  4. customthe mixture is partitioned between ether and excess dilute HCl
  5. washthe organic phase is washed with dilute HCl and brine
  6. dry with materialdried (MgSO4)
  7. customRemoval of the solvent under reduced pressure
  8. waitleft a colorless oil, which
  9. customchromatographed on silica using 10% ethyl acetate in hexane

Sources & evidence

ORD record
ord-eeefef78f71346789090d5d002365aec
Source dataset
uspto-grants-2001_06
Patent number
US06248736B1

Reaction notes

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