Diisopropylamine → 4-Fluoro-3-formyl-2-methoxybenzonitrile

HRID 34015

Reaction equation

HRID 34015 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[C:16]([O:22][CH3:23])[CH:15]=1.[CH:24](N1CCCCC1)=[O:25]>O1CCCC1.CCCCCC.O.C(O)(=O)C>[F:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[C:16]([O:22][CH3:23])[C:15]=1[CH:24]=[O:25]

Participants

9

Reactant 4

HCID 7912DiisopropylamineHCID 174291-PiperidinecarboxaldehydeHCID 27833294-Fluoro-2-methoxybenzonitrileHCID 178418339Butyllithium

Product 1

HCID 230702244-Fluoro-3-formyl-2-methoxybenzonitrileYield 37.2%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

Under nitrogen atmosphere and at −78° C., to a solution of 10.7 g of N,N-diisopropylamine in 150 mL of tetrahydrofuran was added 40 mL of 2.66 M n-butyllithium in n-hexane, stirred at this temperature for 1 hour and 15 minutes, and added dropwise with a solution of 14.5 g of 4-fluoro-2-methoxybenzonitrile obtained by Production example 95 in 50 mL of tetrahydrofuran. After stirring at this temperature for 2 hours, 11.94 g of N-formylpiperidine was added. After stirring at this temperature for 40 minutes, the solution was added with 20 mL of acetic acid at this temperature, added with water at room temperature, and extracted three times with diethyl ether. The organic layer was washed successively with 0.2N hydrochloric acid, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the crude product was purified and separated by silica gel column chromatography, to afford 6.4 g of the title compound 6.4 g as pale yellow crystals.

Workup

  1. stirringAfter stirring at this temperature for 2 hours
  2. stirringAfter stirring at this temperature for 40 minutes
  3. extractionextracted three times with diethyl ether
  4. washThe organic layer was washed successively with 0.2N hydrochloric acid, water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe crude product was purified
  8. customseparated by silica gel column chromatography

Sources & evidence

ORD record
ord-9061043c4833450aa11be9ccb3507016
Source dataset
uspto-grants-2008_09
Patent number
US07429609B2

Linked notes

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