2-(Bromomethyl)-1,3-difluorobenzene → HCID 22482452, compound

HRID 841530Notes

Reaction equation

HRID 841530 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1([C:18]([O:20][CH3:21])=[O:19])[N:13]=[C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]2=[N:10]1.[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=1[CH2:30]Br>>[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=1[CH2:30][N:13]1[C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=2[NH:10][C:9]1([C:3]1[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])[C:18]([O:20][CH3:21])=[O:19]

Participants

3

Reactant 2

HCID 5814352-(Bromomethyl)-1,3-difluorobenzeneHCID 22482462HCID 22482462, compound

Product 1

HCID 22482452HCID 22482452, compoundYield 76%

Procedure

Methyl 2-(2,6-difluorophenyl)benzimidazole-2-carboxylate (4004) (16.15 g, 56.0 mmol) was reacted with 2,6-difluoro-α-bromo-toluene (14.67 g, 70.86 mmol, 125 M%). The crude product was purified by flash chromatography eluting with 2% MeOH/CH2Cl2, and recrystallization from diethylether, yielding white crystals of methyl 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-2-carboxylate (4005) (17.63 g, 42.55 mmol, 76% yield). M.p. 185-186° C. 1H-NMR (200 MHz, CD2Cl2) δ7.94 (dd, J=1.1, 7.6 Hz, 1H, H5), 7.72 (dd, J=1.1, 8.2 Hz, 1H, H7), 7.56 (m, 1H, H4′), 7.37 (dd, J=7.6, 8.2 Hz, 1H, H6), 7.26 (m, 1H, H4″), 7.09 (m, 2H, H3′,5′), 6.82 (m, 2H, H3″,5″), 5.39 (s, 2H, CH2PhF2), 3.95 (s, 3H, CO2CH3).

Workup

  1. customThe crude product was purified by flash chromatography
  2. washeluting with 2% MeOH/CH2Cl2, and recrystallization from diethylether

Sources & evidence

ORD record
ord-0e8bf07170ed412ebae210d8616bf528
Source dataset
uspto-grants-2002_04
Patent number
US06369235B1

Reaction notes

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