Pentamethyldiethylenetriamine → 4-Fluoro-3-[(3-fluorophenyl)-hydroxymethyl)-5-methoxybenzonitrile

HRID 1983508Notes

Reaction equation

HRID 1983508 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:10][CH3:11].CN(CCN(CCN(C)C)C)C.C([Li])CCC.[F:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=1)[CH:33]=[O:34]>O1CCCC1.CCCCCC.O>[F:1][C:2]1[C:3]([O:10][CH3:11])=[CH:4][C:5]([C:6]#[N:7])=[CH:8][C:9]=1[CH:33]([C:32]1[CH:35]=[CH:36][CH:37]=[C:30]([F:29])[CH:31]=1)[OH:34]

Participants

8

Reactant 4

HCID 18196PentamethyldiethylenetriamineHCID 680093-FluorobenzaldehydeHCID 27373654-Fluoro-3-methoxybenzonitrileHCID 178418339Butyllithium

Product 1

HCID 222606574-Fluoro-3-[(3-fluorophenyl)-hydroxymethyl)-5-methoxybenzonitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of 15.0 g of 4-fluoro-3-methoxybenzonitrile and 21.8 ml of N,N,N′,N′,N″-pentamethyldiethylenetriamine in 300 ml tetrahydrofuran was added 65.5 ml of a 1.59 M solution of n-butyllithium in hexane at −78° C. in an atmosphere of nitrogen gas, followed by stirring at the same temperature for 1 hour. At the same temperature, 10.5 ml of 3-fluorobenzaldehyde was added dropwise, followed by stirring at the same temperature for 1 hour. Then, water was added and the mixture was extracted with diethyl ether. The organic layer was washed with saturated aqueous ammonium chloride 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:n-hexane=1:10 to 1:3), to give 7.1 g of the title compound as a colorless oil.

Workup

  1. stirringby stirring at the same temperature for 1 hour
  2. extractionthe mixture was extracted with diethyl ether
  3. washThe organic layer was washed with saturated aqueous ammonium chloride solution and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated
  6. customThe crude product was purified
  7. customseparated by silica gel column chromatography (ethyl acetate:n-hexane=1:10 to 1:3)

Sources & evidence

ORD record
ord-3841f169264148fdaee0ec1d5d3bbbad
Source dataset
uspto-grants-2009_06
Patent number
US07541376B2

Reaction notes

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