Sodium hydride → 2-(4-Chlorophenoxymethyl)-4-benzyloxy-1-[3-[1-(t-butoxycarbonyl)piperidin-4-yl]propyl]-benzimidazole

HRID 1383990Notes

Reaction equation

HRID 1383990 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][CH2:7][C:8]2[NH:9][C:10]3[C:16]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][CH:3]=1.[H-].[Na+].[C:29]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39]([CH2:42][CH2:43][CH2:44]Br)[CH2:38][CH2:37]1)=[O:35])([CH3:32])([CH3:31])[CH3:30]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][C:8]2[N:12]([CH2:44][CH2:43][CH2:42][CH:39]3[CH2:40][CH2:41][N:36]([C:34]([O:33][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:35])[CH2:37][CH2:38]3)[C:11]3[CH:13]=[CH:14][CH:15]=[C:16]([O:17][CH2:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:10]=3[N:9]=2)=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 18409081tert-Butyl 4-(3-bromopropyl)piperidine-1-carboxylateHCID 1784782262-(4-Chlorophenoxymethyl)-4-benzyloxy-benzimidazole

Product 1

HCID 211884662-(4-Chlorophenoxymethyl)-4-benzyloxy-1-[3-[1-(t-butoxycarbonyl)piperidin-4-yl]propyl]-benzimidazoleYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(4-chlorophenoxymethyl)-4-benzyloxy-benzimidazole (720 mg, 1.97 mmol, 1.0 eq) in dry N,N-dimethylformamide (8 ml, 0.25 M) was treated with sodium hydride (60% in mineral oil, 57 mg, 2.30 mmol, 1.2 eq). The resulting mixture was stirred at room temperature for thirty minutes and then 3-[1-(t-butoxycarbonyl)piperidin-4-yl]propyl bromide (7.24 mg, 2.36 mmol, 1.2 eq) was added to the reaction mixture. The resulting mixture was stirred at 70° C. for three hours. The reaction was quenched by the addition of water (1×30 ml). The aqueous fraction was extracted with diethyl ether (1×30 ml). The organic fractions were combined, washed with water (1×30 ml), then brine (1×30 ml), and then dried over sodium sulfate. The solvents were removed in vacuo. The desired title product was further purified by flash chromatography to provide a white foam in 38% yield.

Workup

  1. stirringThe resulting mixture was stirred at 70° C. for three hours
  2. customThe reaction was quenched by the addition of water (1×30 ml)
  3. extractionThe aqueous fraction was extracted with diethyl ether (1×30 ml)
  4. washwashed with water (1×30 ml)
  5. dry with materialbrine (1×30 ml), and then dried over sodium sulfate
  6. customThe solvents were removed in vacuo
  7. customThe desired title product was further purified by flash chromatography
  8. customto provide a white foam in 38% yield

Sources & evidence

ORD record
ord-8164c18d5b1a4e87804791fb7357010c
Source dataset
uspto-grants-2001_07
Patent number
US06255494B1

Reaction notes

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