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

HRID 1383984Notes

Reaction equation

HRID 1383984 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+].[OH2:22].Cl.Cl.N1(CC[CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][N:34]2[C:39](CCCCN2C3C=CC=C(C)C=3N=C2COC2C=CC(Cl)=CC=2)=[O:40])CCCCC1.[C:64]([O:68][C:69]([N:71]1[CH2:76][CH2:75][CH2:74][CH:73]([CH2:77][CH2:78][CH2:79]Br)[CH2:72]1)=[O:70])([CH3:67])([CH3:66])[CH3:65]>CN(C)C=O>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([O:12][CH2:11][C:8]2[N:7]([CH2:79][CH2:78][CH2:77][CH:73]3[CH2:74][CH2:75][CH2:76][N:71]([C:69]([O:68][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:70])[CH2:72]3)[C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([O:1][CH2:72][CH2:73][CH2:74][CH:36]4[CH2:37][CH2:38][CH2:33][N:34]([C:39]([O:40][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:22])[CH2:35]4)[C:10]=3[N:9]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 18515798tert-Butyl 3-(3-bromopropyl)piperidine-1-carboxylateHCID 1317227611-[4-[[2-[(2-Piperidin-1-yl)ethyl]piperidin-1-yl]carbonyl]butyl]-2-[(4-chlorophenoxy)methyl]-4-methylbenzimidazole dihydrochloride salt monohydrateHCID 178515906HCID 178515906, compound

Product 1

HCID 211887722-(4-Chlorophenoxymethyl)-4-[3-[1-(t-butoxycarbonyl)piperidin-3-yl]propoxy]-1-[3-[1-(t-butoxycarbonyl)piperidin-3-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 (R) 3-[1-(t-butoxycarbonyl)piperidin-3-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.

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-6e44823555dc4b93aa52d25230a98931
Source dataset
uspto-grants-2001_07
Patent number
US06255494B1

Reaction notes

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