3-Bromo-4-fluorobenzaldehyde → 3-Cyclopropyl-4-fluorobenzaldehyde

HRID 453528Notes

Reaction equation

HRID 453528 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.Br[C:7]1[CH:8]=[C:9]([CH:12]=[CH:13][C:14]=1[F:15])[CH:10]=[O:11]>C1COCC1.[Cl-].[Zn+2].[Cl-].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>[CH:1]1([C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][C:14]=2[F:15])[CH:10]=[O:11])[CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 1736043-Bromo-4-fluorobenzaldehydeHCID 178418630HCID 178418630, compound

Product 1

HCID 574343473-Cyclopropyl-4-fluorobenzaldehydeYield 49.5%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A flask was charged with cyclopropyl magnesium bromide (29.6 ml, 14.8 mmol) and placed under nitrogen. Zinc chloride (14.8 ml, 14.8 mmol) was added and the reaction was stirred for 20 minutes. 3-Bromo-4-fluorobenzaldehyde (1.0 g, 4.93 mmol) and bis(tri-t-butylphosphine)palladium (0) (0.126 g, 0.246 mmol) were diluted in 600 μL of THF and added to the reaction mixture. After stirring for 4 hours, the reaction was heated to 50° C. and stirred overnight. The reaction was cooled and quenched with saturated NH4Cl and extracted with DCM. The organic layer was dried over MgSO4, filtered and concentrated. The material was purified using a biotage 40M cartridge eluting with hexanes:ethyl acetate (4:1) to yield 3-cyclopropyl-4-fluorobenzaldehyde (400 mg, 49.5% yield)

Workup

  1. additionadded to the reaction mixture
  2. stirringAfter stirring for 4 hours
  3. stirringstirred overnight
  4. temperatureThe reaction was cooled
  5. customquenched with saturated NH4Cl
  6. extractionextracted with DCM
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe material was purified
  11. washeluting with hexanes:ethyl acetate (4:1)

Sources & evidence

ORD record
ord-226347ba743f4da583217f5678573b73
Source dataset
uspto-grants-2013_07
Patent number
US08492437B2

Reaction notes

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