Hydrochloric Acid → 5-Bromo-2-fluoro-4-methylbenzaldehyde

HRID 402274Notes

Reaction equation

HRID 402274 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH3:9].C([N-]C(C)C)(C)C.[Li+].CN([CH:21]=[O:22])C.Cl>O1CCCC1.O>[Br:1][C:2]1[C:3]([CH3:9])=[CH:4][C:5]([F:8])=[C:6]([CH:7]=1)[CH:21]=[O:22]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 967432-Bromo-5-fluorotolueneHCID 2724682Lithium diisopropylamide

Product 1

HCID 447549105-Bromo-2-fluoro-4-methylbenzaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-bromo-5-fluorotoluene (20 g) in dry tetrahydrofuran (200 ml) was added dropwise lithium diisopropylamide (2.0 M, heptan-tetrohydrofuran-ethylbenzene solution, 52.9 ml) under argon atmosphere at −78° C. After stirring as such for 2 hours, a solution of DMF (41 ml) in dry tetrahydrofuran (50 ml) was added dropwise. The mixture was returned to room temperature and stirred for 1 hour. Then, water was added and the mixture was neutralized with 1N hydrochloric acid. After extraction with ethyl acetate, the extract was washed with saturated brine and dried with magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=24:1) and re-crystallized from hexane-ethyl acetate to give 5-bromo-2-fluoro-4-methylbenzaldehyde (9.39 g).

Workup

  1. customwas returned to room temperature
  2. stirringstirred for 1 hour
  3. extractionAfter extraction with ethyl acetate
  4. washthe extract was washed with saturated brine
  5. dry with materialdried with magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=24:1)
  8. customre-crystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-efb3461c19934f4ca0af041b1d43a7c4
Source dataset
uspto-grants-2014_06
Patent number
US08741943B2

Reaction notes

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