Methyl 4-bromo-3-fluorobenzoate → Methyl 3-fluoro-4-isobutylbenzoate

HRID 1443407Notes

Reaction equation

HRID 1443407 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[F:12].[Br-].[CH2:14]([Zn+])[CH:15]([CH3:17])[CH3:16]>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:12][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=1[CH2:14][CH:15]([CH3:17])[CH3:16])[C:6]([O:8][CH3:9])=[O:7]

Participants

5

Reactant 2

HCID 21951878Methyl 4-bromo-3-fluorobenzoateHCID 178448254HCID 178448254, compound

Product 1

HCID 54062470Methyl 3-fluoro-4-isobutylbenzoateYield 84%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-bromo-3-fluorobenzoate (322 mg, 1.38 mmol) and isobutylzinc bromide (4.1 mL, 0.5 M in THF) in 10 mL of THF was added bis(tri-tert-butylphosphine)palladium(0) (14 mg, 0.03 mmol). The mixture was flushed with nitrogen three times and then stirred at rt overnight. The reaction was quenched by adding 5.0 mL of 1.0 N HCl solution and extracted with Et2O (3×20 mL). Organic layers were combined, washed with brine, dried over MgSO4, and concentrated. Chromatography on a Biotage 40+S cartridge using 1:99 v/v EtOAc/hexanes as the eluant afforded 243 mg (84%) of the title compound: 1H NMR δ 0.92 (d, J=6.6, 6H), 1.93 (m, 1H), 2.56 (d, J=6.1, 2H), 3.91 (s, 31H), 7.21 (t, J=7.6, 11H), 7.67 (dd, J=1.5, 10.2, 11H), 7.74 (dd, J=1.6, 7.8, 11H).

Workup

  1. customThe mixture was flushed with nitrogen three times
  2. customThe reaction was quenched
  3. additionby adding 5.0 mL of 1.0 N HCl solution
  4. extractionextracted with Et2O (3×20 mL)
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ba9c6d75bd5943bfbaf736d5249dd33c
Source dataset
uspto-grants-2010_02
Patent number
US07659294B2

Reaction notes

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