Dichloromethane → HCID 492682, compound

HRID 841553Notes

Reaction equation

HRID 841553 reaction equation
C(Cl)Cl.[F:4][C:5]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:6]=1[CH2:7][N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[C:16]([CH2:17][OH:18])[C:11]=2[N:10]=[C:9]1[C:19]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=1[F:26]>N1C=CC=CC=1.N1C=CC=CC=1.C(Cl)Cl>[F:4][C:5]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:6]=1[CH2:7][N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[C:16]([CH:17]=[O:18])[C:11]=2[N:10]=[C:9]1[C:19]1[C:20]([F:26])=[CH:21][CH:22]=[CH:23][C:24]=1[F:25]

Participants

5

Reactant 2

HCID 6344DichloromethaneHCID 4926811-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxymethylbenzimidazole

Product 1

HCID 492682HCID 492682, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 21875418Pyridine methylene chlorideSolvent

Procedure

To CrO3 (1.26 g) dissolved in pyridine (1.0 mL) and CH2Cl2 (9.0 mL) was added 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-hydroxylmethylbenzimidazole (Example 112) (0.49 g, 1.27 mmol) dissolved in pyridine:CH2Cl2 (1:1) (2 mL). After stirring for 6 h, the reaction was filtered. The filtrate was diluted with CH2Cl2, and washed with NaHCO3 (sat. soln) and NaCl (sat. aq). The combined washings were dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash chromatography eluting with 1% methanol/CH2Cl2. Recrystallization from diethylether:hexane (3:1) yielded white crystals of 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-benzimidazole-4-carbaldehyde (0.38 g, 0.99 mmol, 78% yield). M.p. 151-153° C. 1H-NMR (300 MHz, CD2Cl2): δ10.82 (d, J=0.6 Hz, 1H, CHO), 7.83 (dd, J=7.5, 1.1 Hz, 1H, H7), 7.78 (dd, J=8.1, 1.1 Hz, H5), 7.58 (m, 1H, H4′), 7.44 (ddd, J=8.1, 7.5, 0.6 Hz, 1H, H6), 7.27 (m, 1H, H4″), 7.11 (m, 2H, H3′,5′), 6.84 (m, 2H, H3″,5″), 5.42 (s, 2H, CH2PhF2).

Workup

  1. filtrationthe reaction was filtered
  2. additionThe filtrate was diluted with CH2Cl2
  3. washwashed with NaHCO3 (sat. soln) and NaCl (sat. aq)
  4. dry with materialThe combined washings were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography
  8. washeluting with 1% methanol/CH2Cl2
  9. customRecrystallization from diethylether:hexane (3:1)

Sources & evidence

ORD record
ord-a459058fabab46a596b24a8b58880afa
Source dataset
uspto-grants-2002_04
Patent number
US06369235B1

Reaction notes

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