3-Fluoro-4-nitrobenzaldehyde → 2-(4-tert-Butyl-phenyl)-4-[4-(3-fluoro-4-nitro-benzyl)-piperazin-1-yl]-1H-benzoimidazole

HRID 642880Notes

Reaction equation

HRID 642880 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:15][C:14]3[CH:16]=[CH:17][CH:18]=[C:19]([N:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[C:13]=3[N:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[F:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[N+:35]([O-:37])=[O:36])[CH:30]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN1CCCC1=O.C(OCC)(=O)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[NH:15][C:14]3[CH:16]=[CH:17][CH:18]=[C:19]([N:20]4[CH2:25][CH2:24][N:23]([CH2:30][C:29]5[CH:32]=[CH:33][C:34]([N+:35]([O-:37])=[O:36])=[C:27]([F:26])[CH:28]=5)[CH2:22][CH2:21]4)[C:13]=3[N:12]=2)=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 38081203-Fluoro-4-nitrobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 592588032-(4-tert-Butyl-phenyl)-4-piperazin-1-yl-1H-benzoimidazole

Product 1

HCID 585927062-(4-tert-Butyl-phenyl)-4-[4-(3-fluoro-4-nitro-benzyl)-piperazin-1-yl]-1H-benzoimidazoleYield 68.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirring solution of 2-(4-tert-Butyl-phenyl)-4-piperazin-1-yl-1H-benzoimidazole (0.857 g, 2.56 mMol) and 3-Fluoro-4-nitro-benzaldehyde (0.52 g, 3.07 mMol) in N-methylpyrrolidinone (20 mL) was added sodium triacetoxyborohydride (1.36 g, 6.40 mMol) and the solution stirred overnight. Upon arrival the solution was diluted with ethyl acetate (200 mL). The mixture was washed with saturated sodium bicarbonate solution (75 mL), water (75 mL), and brine (75 mL). The organic layer was then dried with magnesium sulfate, filtered, concentrated, and purified by flash column chromatography on silica gel using 40% ethyl acetate in hexane as the eluant to yield 850 mg (68% yield) of 2-(4-tert-Butyl-phenyl)-4-[4-(3-fluoro-4-nitro-benzyl)-piperazin-1-yl]-1H-benzoimidazole as a light yellow solid. 1H NMR (DMSO-d6): δ=12.69 (s, 1H), 8.16 (t, 1H, J=8.2 Hz), 8.04 (d, 2H, J=8.5 Hz), 7.59 (m, 1H), 7.55 (d, 2H, J=8.5 Hz), 7.47 (d, 1H, J=8.6 Hz), 7.03 (m, 2H), 6.50 (dd, 1H, J=7.0, 1.8 Hz), 3.71 (s, 2H), 3.60 (br s, 4H), 2.66 (br s, 4H), 1.33 (s, 9H). LC/MS (Method A), rt=1.24 mins., purity=100%, calculated mass=487, [M+H]+=488, [M−H]−=486.

Workup

  1. washThe mixture was washed with saturated sodium bicarbonate solution (75 mL), water (75 mL), and brine (75 mL)
  2. dry with materialThe organic layer was then dried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by flash column chromatography on silica gel using 40% ethyl acetate in hexane as the eluant

Sources & evidence

ORD record
ord-b506f1e2c2f94482a18c0ff4c0e8b3ff
Source dataset
uspto-grants-2010_04
Patent number
US07696210B2

Reaction notes

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