Diisopropylamine → HCID 22261000, compound

HRID 1610057Notes

Reaction equation

HRID 1610057 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[F:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1.[F:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[CH:26]=[O:27].[Cl-].[NH4+]>CCCCCC.O1CCCC1>[F:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=1[CH:26]([C:25]1[CH:28]=[CH:29][CH:30]=[C:23]([F:22])[CH:24]=1)[OH:27]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 145174-FluorobenzonitrileHCID 25517Ammonium ChlorideHCID 680093-FluorobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 22261000HCID 22261000, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

In an atmosphere of nitrogen gas, 76.3 ml of 1.56 M solution of n-butyllithium in hexane was added to a solution of 11.1 g of N,N-diisopropylamine in 200 ml tetrahydrofuran under ice-cooling, and the mixture was stirred at the same temperature for 15 minutes. After cooling to −78° C., a solution of 12.1 g of 4-fluorobenzonitrile in 40 ml tetrahydrofuran was added dropwise. After stirring at the same temperature for 45 minutes, 10.6 ml of 3-fluorobenzaldehyde was added dropwise. After stirring at the same temperature for 25 minutes, saturated aqueous ammonium chloride solution was added and the solvent was removed. To the residue was added 150 ml of ethyl acetate, and the mixture was sequentially washed with 1 N hydrochloric acid, water, saturated aqueous sodium hydrogencarbonate solution and brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The crude product was purified and separated by silica gel column chromatography (ethyl acetate:toluene=3:97 to 1:19), and the resulting crystals were recrystallized from diisopropyl ether-hexane, to give 12.7 g of the title compound as pale yellow needles.

Workup

  1. temperaturecooling
  2. stirringAfter stirring at the same temperature for 45 minutes
  3. stirringAfter stirring at the same temperature for 25 minutes
  4. customthe solvent was removed
  5. additionTo the residue was added 150 ml of ethyl acetate
  6. washthe mixture was sequentially washed with 1 N hydrochloric acid, water, saturated aqueous sodium hydrogencarbonate solution and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated
  9. customThe crude product was purified
  10. customseparated by silica gel column chromatography (ethyl acetate:toluene=3:97 to 1:19)
  11. customthe resulting crystals were recrystallized from diisopropyl ether-hexane

Sources & evidence

ORD record
ord-d654e0bcc9ff4d59a25615e55e4925d1
Source dataset
uspto-grants-2006_01
Patent number
US06982274B2

Reaction notes

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