Dimethylformamide → 5-Fluoro-7-benzofurancarboxaldehyde

HRID 1371745Notes

Reaction equation

HRID 1371745 reaction equation
Br[C:2]1[C:10]2[O:9][CH:8]=[CH:7][C:6]=2[CH:5]=[C:4]([F:11])[CH:3]=1.C([Li])CCC.CN(C)[CH:19]=[O:20].[Cl-].[NH4+]>O1CCCC1.CCCCC>[F:11][C:4]1[CH:3]=[C:2]([CH:19]=[O:20])[C:10]2[O:9][CH:8]=[CH:7][C:6]=2[CH:5]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 221448167-Bromo-5-fluoro-1-benzofuranHCID 178418339Butyllithium

Product 1

HCID 179854595-Fluoro-7-benzofurancarboxaldehydeYield 30%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-97.5 °C

Procedure

7-Bromo-5-fluoro-benzofuran (7 g, 32 mmol, Step B) was dissolved in a mixture of tetrahydrofuran (350 mL) and pentane (100 mL), cooled to −95 to −100° C., and treated with n-butyl lithium (14 mL, 35 mmol, 2.5M in hexane, Aldrich). After stirring for 5 minutes, a solution of dimethylformamide (5 mL) in tetrahydrofuran (15 mL) was added dropwise and the reaction temperature raised to −20° C. This was treated with aqueous ammonium chloride (50 mL) and stirred for 0.5 hour at ambient temperature. The reaction mixture was concentrated in vacuo and diluted with hexane. The organic fraction was washed with water and dried (Na2SO4). Removal of solvent afforded crude 5-fluoro-benzofuran-7-carbaldehyde (˜30%) as an oil. Purification was by silica gel chromatography (5–10% ethyl ether/hexane). HRMS, observed: 163.0201; Calcd for (M+H)+: 163.0195

Workup

  1. temperaturethe reaction temperature raised to −20° C
  2. stirringstirred for 0.5 hour at ambient temperature
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. additiondiluted with hexane
  5. washThe organic fraction was washed with water
  6. dry with materialdried (Na2SO4)
  7. customRemoval of solvent

Sources & evidence

ORD record
ord-7361e1c59df343a09f486cc3fa206eb2
Source dataset
uspto-grants-2007_01
Patent number
US07157455B2

Reaction notes

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