Tetrahydrofuran → 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-benzimidazoyl-2-propanol

HRID 841551Notes

Reaction equation

HRID 841551 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:15])[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].[CH3:31][Li].[CH2:33]1[CH2:37][O:36]CC1>CCOC(C)=O>[F:25][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]([F:24])[C:18]=1[CH2:6][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([C:14]([CH2:31][CH:37]([OH:36])[CH3:33])=[O:15])[C:8]=2[N:7]=[C:4]1[C:3]1[C:2]([F:1])=[CH:29][CH:28]=[CH:27][C:26]=1[F:30]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 492679Methyl 2-(2,6-difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazole-4-carboxylateHCID 178418348HCID 178418348, compound

Product 1

HCID 224824561-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-benzimidazoyl-2-propanolYield 55%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To methyl 1-(2,6-difluorobenyl)-2-(2,6-difluorophenyl)benzimidazole-4-carboxylate (Example 102) (1.02 g, 2.46 mmol) suspended in THF (5 mL) was added 1.4 M methyl lithium (0.95 mL). After 0.5 h, the reaction was diluted with EtOAc and washed with NaHSO4 (10% soln) and NaCl(sat. aq). The combined washings were dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography eluting with 1:1 ethylacetate/hexane and recrystallization from hexane, yielding white crystals of 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-benzimidazoyl-2-propanol (0.11 g, 0.27 mmol, 55% yield). M.p. 149-150° C. 1H-NMR (200 MHz, CD2Cl2): δ7.55 (m, 1H, H4′), 7.48 (d, J=8.1 Hz, 1H, H5), 7.25 (m, 2H, H6,4″), 7.16 (dd, J=1.1, 7.6 Hz, 1H, H7), 7.10 (m, 2H, H3′,5′), 6.82 (m, 2H, H3″,5″), 5.82 (s, 1H, OH), 5.37 (s, 2H, CH2PhF2), 1.67 (s, 6H, CH3). Anal. (C23H18F4N2O) C,H,N.

Workup

  1. washwashed with NaHSO4 (10% soln) and NaCl(sat. aq)
  2. dry with materialThe combined washings were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography
  6. washeluting with 1:1 ethylacetate/hexane and recrystallization from hexane

Sources & evidence

ORD record
ord-5413a3607f3d4ce085b14b2bbf9ff927
Source dataset
uspto-grants-2002_04
Patent number
US06369235B1

Reaction notes

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