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

HRID 2182106노트

반응식

HRID 2182106 반응식
[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]

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 6212Chloroform용매2회

실험 절차

To 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxylmethyl-benzimidazole (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): δ 7.55 (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).

후처리

  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)

출처 및 근거

ORD 기록
ord-1f1c864bcc3545c1be40940e32bbbfd5
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06894068B2

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