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

HRID 1383980Notes

Reaction equation

HRID 1383980 reaction equation
[OH:1][C:2]1[C:10]2[NH:9][C:8]([CH2:11][O:12][C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)=[N:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([CH2:35][CH2:36][CH2:37]Br)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]>CN(C)C=O>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([O:12][CH2:11][C:8]2[N:7]([CH2:37][CH2:36][CH2:35][CH:32]3[CH2:33][CH2:34][N:29]([C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:28])[CH2:30][CH2:31]3)[C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([O:1][CH2:37][CH2:36][CH2:35][CH:32]4[CH2:33][CH2:34][N:29]([C:27]([O:26][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:28])[CH2:30][CH2:31]4)[C:10]=3[N:9]=2)=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 18409081tert-Butyl 4-(3-bromopropyl)piperidine-1-carboxylateHCID 178515906HCID 178515906, compound

Product 1

HCID 211885412-(4-Chlorophenoxymethyl)[3-[1-(t-butoxycarbonyl)piperidin-4-yl]propoxy]-1-[3-[1-(t-butoxycarbonyl)piperidin-4-yl]propyl]benzimidazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-hydroxy-2-(4-chlorophenoxymethyl)benzimidazole (500 mg, 1.82 mmol) in dry N,N-dimethylformamide (8 ml) was treated with sodium hydride (60% in mineral oil, 162 mg, 4.0 mmol, 2.2 eq). The resulting mixture was stirred at room temperature under a stream of nitrogen for about one hour. To this reaction mixture 3-[1-(t-butoxycarbonyl)piperidin-4-yl)propyl bromide (4.0 mmol, 2.2 eq) was added and the resulting mixture was stirred for three hours at 70° C. The reaction was quenched by the addition of 10 ml of water. The aqueous fraction was extracted with ethyl acetate (3×10 ml). The organic fractions were combined and washed with water (2×10 ml), and then brine (1×10 ml), and then dried over magnesium sulfate. The solvents were removed in vacuo to yield a light brownish crude material. The desired title product was further purified by flash chromatography. There is some substitution at the 7-position of the benzimidazole present, although the 4-substituted is the major isomer.

Workup

  1. stirringthe resulting mixture was stirred for three hours at 70° C
  2. customThe reaction was quenched by the addition of 10 ml of water
  3. extractionThe aqueous fraction was extracted with ethyl acetate (3×10 ml)
  4. washwashed with water (2×10 ml)
  5. dry with materialbrine (1×10 ml), and then dried over magnesium sulfate
  6. customThe solvents were removed in vacuo

Sources & evidence

ORD record
ord-062a126c4340456ca2af16d87f5ee44f
Source dataset
uspto-grants-2001_07
Patent number
US06255494B1

Reaction notes

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