Methyl 2-(2,6-difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazole-4-carboxylate → 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrile

HRID 841548Notes

Reaction equation

HRID 841548 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([C:14](OC)=O)[C:8]=2[N:7]=[C:6]1[C:18]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=1[F:25].[Al]([NH2:34])(C)C>C1(C)C(C)=CC=CC=1>[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([C:14]#[N:34])[C:8]=2[N:7]=[C:6]1[C:18]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=1[F:25]

Participants

4

Reactant 2

HCID 492679Methyl 2-(2,6-difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazole-4-carboxylateHCID 16689643Aminodimethyl aluminium

Product 1

HCID 98647011-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrileYield 61%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

To methyl 1-(2,6-difluorobenyl)-2-(2,6-difluorophenyl)benzimidazole-4-carboxylate (Example 102) (1.02 g, 2.46 mmol) suspended in xylene (60 mL) was added freshly prepared 1.0 M AlMe2NH2 (20 mL). After 3 h at reflux, the reaction was concentrated. The residue was redissolved in CH2Cl2 and washed with NaHSO4 (10% soln), NaHCO3 (sat. aq) and NaCl (sat. aq). The combined washings were dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography eluting with 2% methanol/CH2Cl2 and recrystallization from diethylether/hexane (3:1), yielding white crystals of 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)- benzimidazole-4-carbonitrile (1.72 g, 4.51 mmol, 61% yield). M.p. 156-157° C.; 1H NMR (200 MHz, CD2Cl2): δ7.76 (dd, J=1.0, 8.6 Hz, 1H, H5), 7.63 (dd, J=1.0, 7.6 Hz, 1H, H7), 7.58 (m, 1H, H4′), 7.37 (dd, J=7.6, 8.6 Hz, 1H, H6), 7.28 (m, 1H, H4″), 7.11 (m, 2H, H3′,5′), 6.83 (m, 2H, H3″,5″), 5.40 (s, 2H, CH2PhF2).

Workup

  1. temperatureAfter 3 h at reflux
  2. concentrationthe reaction was concentrated
  3. dissolutionThe residue was redissolved in CH2Cl2
  4. washwashed with NaHSO4 (10% soln), NaHCO3 (sat. aq) and NaCl (sat. aq)
  5. dry with materialThe combined washings were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography
  9. washeluting with 2% methanol/CH2Cl2 and recrystallization from diethylether/hexane (3:1)

Sources & evidence

ORD record
ord-92a8004ae7e6413f9134a4d6524ad6c0
Source dataset
uspto-grants-2002_04
Patent number
US06369235B1

Reaction notes

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