Isobutyryl chloride → Ethyl 4-isobutyrylbenzoate

HRID 1049086Notes

Reaction equation

HRID 1049086 reaction equation
[I-].[CH2:2]([O:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([Zn+])=[CH:9][CH:8]=1)=[O:6])[CH3:3].[C:14](Cl)(=[O:18])[CH:15]([CH3:17])[CH3:16]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[C:14]([C:10]1[CH:11]=[CH:12][C:7]([C:5]([O:4][CH2:2][CH3:3])=[O:6])=[CH:8][CH:9]=1)(=[O:18])[CH:15]([CH3:17])[CH3:16]

Participants

5

Reactant 2

HCID 62325Isobutyryl chlorideHCID 178469116HCID 178469116, compound

Product 1

HCID 45116516Ethyl 4-isobutyrylbenzoateYield 90.4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a 100-mL round-bottom flask was added THF (25 mL). The solvent was bubbled with nitrogen for a few minutes then cooled to 0° C. and added bis(triphenylphosphine)palladium(II) chloride (0.44 g, 0.63 mmol) followed by 4-(ethoxycarbonyl)phenylzinciodide (25.0 mL, 12.5 mmol; 0.50 M in THF). After stirred at at 0° C. for 15 min, isobutyryl chloride (1.32 mL, 12.5 mmol) was added and the resulting mixture was stirred at 0° C. for 2 h. The reaction was quenched with slow addition of 1 N HCl and extracted with EtOAc (3×100 mL). After separation, combined organic extracts were washed with sat. NaHCO3, water, brine, dried (MgSO4), and concentrated. Flash column chromatography (EtOAc:hexanes, 0:1 to 1:9) afforded ethyl 4-isobutyrylbenzoate (2.49 g, 90%) as a slight-brown oil. LC-MS: (FA) ES+ 221; 1H NMR (CDCl3, 400 MHz) δ8.13 (d, J=8.5 Hz, 2H), 7.99 (d, J=8.5 Hz, 2H), 4.40 (q, J=7.2 Hz, 2H), 3.56 (m, 1H), 1.42 (t, J=7.2 Hz, 3H), 1.23 (d, J=7.2 Hz, 6H).

Workup

  1. customThe solvent was bubbled with nitrogen for a few minutes
  2. stirringthe resulting mixture was stirred at 0° C. for 2 h
  3. customThe reaction was quenched with slow addition of 1 N HCl
  4. extractionextracted with EtOAc (3×100 mL)
  5. customAfter separation
  6. washwere washed with sat. NaHCO3, water, brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-bbde496a7d3b425e846f36c9b5526b33
Source dataset
uspto-grants-2016_07
Patent number
US09382197B2

Reaction notes

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