Dimethylformamide → tert-Butyl 2-fluoro-4-formylbenzoate

HRID 2102924Notes

Reaction equation

HRID 2102924 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[C:4]([F:15])[CH:3]=1.[Li]CCCC.CN([CH:24]=[O:25])C>C1COCC1>[F:15][C:4]1[CH:3]=[C:2]([CH:24]=[O:25])[CH:14]=[CH:13][C:5]=1[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 46738774tert-Butyl 4-bromo-2-fluorobenzoateHCID 178418339Butyllithium

Product 1

HCID 86607392tert-Butyl 2-fluoro-4-formylbenzoateYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of tert-butyl 4-bromo-2-fluorobenzoate (1.5 g, 5.45 mmol) in THF (70 mL) at −100° C. under argon was carefully added BuLi (2.5 M in hexane, 2.3 mL, 5.75 mmol). The mixture was kept at −100° C. to −80° C. for 1 h and then DMF (1.0 mL) in THF (5 mL) was added. After 1 h, the mixture was warmed to 0° C. and quenched by adding sat. aq NH4Cl, and extracted with EtOAc. The organic layer was separated, washed with brine, dried (MgSO4), and concentrated under vacuum. The residue was purified by column chromatography on silica gel using EtOAc/hexane (0-10%) as eluent to give the product (750 mg, 61%) as a white solid.

Workup

  1. customat −100° C.
  2. waitAfter 1 h
  3. customquenched
  4. additionby adding sat. aq NH4Cl
  5. extractionextracted with EtOAc
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-8a0c2969f92b4ff8b3bf8bbf93c882f2
Source dataset
uspto-grants-2009_08
Patent number
US07576099B2

Reaction notes

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