Dimethylformamide → 2-Bromo-4-fluoro-3-formylbenzoic acid tert-butyl ester

HRID 79009Notes

Reaction equation

HRID 79009 reaction equation
[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[Br:14])([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].CN([CH:27]=[O:28])C>C1COCC1>[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([CH:27]=[O:28])[C:8]=1[Br:14])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 2724682Lithium diisopropylamideHCID 26986095tert-Butyl 2-bromo-4-fluorobenzoate

Product 1

HCID 575229892-Bromo-4-fluoro-3-formylbenzoic acid tert-butyl esterYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-bromo-4-fluoro-benzoic acid tert-butyl ester (10.0 g, 36 mmol) in THF (100 mL) at −78° C. under an atmosphere of nitrogen was added lithium diisopropylamide (1.8M solution, 20 mL, 36 mmol) dropwise. The reaction mixture was stirred for 1.25 hours before adding DMF (10 mL) then stirred for a further 10 minutes before quenching with acetic acid (3 mL). The products were partitioned between ethyl acetate and water, the organic layer was separated, washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to give a yellow oil which crystallized on standing. The crude product was triturated in cyclohexane to give the title compound as a yellow solid (6.8 g, 62%). 1H NMR (CDCl3, 400 MHz) 10.38 (1H, s), 7.80-7.73 (1H, m), 7.17 (1H, t, J=9.09 Hz), 1.62 (9H, s).

Workup

  1. stirringthen stirred for a further 10 minutes
  2. custombefore quenching with acetic acid (3 mL)
  3. customThe products were partitioned between ethyl acetate and water
  4. customthe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a yellow oil which
  10. customcrystallized
  11. customThe crude product was triturated in cyclohexane

Sources & evidence

ORD record
ord-a7bc02063c2c46bfbace9be5dbcd67f2
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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