Thionyl Chloride → 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-chloromethylbenzimidazole

HRID 841554Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 841554
[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([CH2:14]O)[C:8]=2[N:7]=[C:6]1[C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=1[F:23].O=S(Cl)[Cl:31]>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([CH2:14][Cl:31])[C:8]=2[N:7]=[C:6]1[C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=1[F:23]

Komponenten

4

Edukt 2

HCID 24386Thionyl ChlorideHCID 4926811-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxymethylbenzimidazole

Produkt 1

HCID 4926831-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-chloromethylbenzimidazoleAusbeute 92 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6212ChloroformLösungsmittel2×

Versuchsvorschrift

To 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxylmethylbenzimidazole (Example 112) (0.54 g, 1.40 mmol) dissolved in CHCl3 (3.0 mL) was added SOCl2 (0.15 mL, 2.06 mmol, 150 M%). After 3 h at room temperature, the reaction was diluted with CHCl3, and washed with NaHCO3 (sat. soln) and NaCl (sat. aq). The combined washings were dried (Na2SO4), filtered and concentrated. The product was purified by flash chromatography eluting with 1% MeOH/CH2Cl2. Recrystallization from diethylether:hexane (3:1) yielded white crystals of 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-chloromethylbenzimidazole (0.52 g, 1.28 mmol, 92% yield). M.p. 143-144° C. 1H-NMR (300 MHz, CD2Cl2): δ7.55 (m, 1H, H4′), 7.48 (dd, J=7.7, 1.1 Hz, 1H, H7), 7.36 (dd, J=7.6 Hz, 1.1 Hz, 1H, H5), 7.30 (dd, J=7.7, 7.6 Hz, 1H, H6), 7.25 (m, 1H, H4″), 7.09 (m, 2H, H3′,5′), 6.82 )m, 2H, H3″,5″), 5.36 (s, 2H, CH2PhF2), 5.07 (s, 2H, CH2Cl).

Aufarbeitung

  1. washwashed with NaHCO3 (sat. soln) and NaCl (sat. aq)
  2. dry with materialThe combined washings were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe product was purified by flash chromatography
  6. washeluting with 1% MeOH/CH2Cl2
  7. customRecrystallization from diethylether:hexane (3:1)

Quellen und Nachweise

ORD-Eintrag
ord-8d37476b677d4f05b65dffe4aa9046b7
Quelldatensatz
uspto-grants-2002_04
Patentnummer
US06369235B1

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