4-Methoxybenzylamine → 3,5-Difluoro-4-(4-methoxy-benzylamino)-benzonitrile

HRID 912164Notes

Reaction equation

HRID 912164 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1F)[C:5]#[N:6].C(N(C(C)C)C(C)C)C.[CH3:21][O:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][NH2:28])=[CH:25][CH:24]=1>C(#N)C>[F:11][C:8]1[CH:7]=[C:4]([CH:3]=[C:2]([F:1])[C:9]=1[NH:28][CH2:27][C:26]1[CH:29]=[CH:30][C:23]([O:22][CH3:21])=[CH:24][CH:25]=1)[C:5]#[N:6]

Participants

5

Reactant 3

HCID 754524-MethoxybenzylamineHCID 81531DiisopropylethylamineHCID 5938143,4,5-Trifluorobenzonitrile

Product 1

HCID 592447423,5-Difluoro-4-(4-methoxy-benzylamino)-benzonitrileYield 100%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To acetonitrile solution (500 ml) of 3,4,5-trifluoro-benzonitrile (15.0 g, 95.5 mmol), N-ethyldiisopropylamine (33.3 ml, 191 mmol) and 4-methoxy-benzylamine (24.9 ml, 191 mmol) were added, followed by refluxing for 21 hours. The solvent was distilled off under reduced pressure, followed by dissolution in ethyl acetate (500 ml), which was washed with saturated aqueous sodium chloride solution (200 ml). After the organic layer was dried over sodium sulfate, the solvent was distilled off under reduced pressure. This was purified by silica gel column chromatography (dichloromethane), to obtain the desired compound (26.2 g, quant.).

Workup

  1. temperatureby refluxing for 21 hours
  2. distillationThe solvent was distilled off under reduced pressure
  3. dissolutionfollowed by dissolution in ethyl acetate (500 ml)
  4. washwhich was washed with saturated aqueous sodium chloride solution (200 ml)
  5. dry with materialAfter the organic layer was dried over sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThis was purified by silica gel column chromatography (dichloromethane)

Sources & evidence

ORD record
ord-8d5fb1958a2a40f1bdea847b729c7a0c
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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