Sodium hydride → (RS) 2-(4-chlorophenoxymethyl)-4-[2-[1-(t-butoxycarbonyl)piperidin-3-yl]ethoxy]-1-[3-[1-(t-butoxycarbonyl)piperidin-3-yl]propyl]-benzimidazole

HRID 1383993Notes

Reaction equation

HRID 1383993 reaction equation
[Cl:1][C:2]1[CH:35]=[CH:34][C:5]([O:6][CH2:7][C:8]2[N:12]([CH2:13][CH2:14][CH2:15][CH:16]3[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]3)[C:11]3[CH:29]=[CH:30][CH:31]=[C:32]([OH:33])[C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][CH2:48][CH:47]([CH2:51][CH2:52]Br)[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][C:8]2[N:12]([CH2:13][CH2:14][CH2:15][CH:16]3[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]3)[C:11]3[CH:29]=[CH:30][CH:31]=[C:32]([O:33][CH2:52][CH2:51][CH:47]4[CH2:48][CH2:49][CH2:50][N:45]([C:43]([O:42][C:38]([CH3:39])([CH3:41])[CH3:40])=[O:44])[CH2:46]4)[C:10]=3[N:9]=2)=[CH:34][CH:35]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 21188576HCID 21188576, compoundHCID 21188829tert-Butyl 3-(2-bromoethyl)piperidine-1-carboxylate

Product 1

HCID 10842515(RS) 2-(4-chlorophenoxymethyl)-4-[2-[1-(t-butoxycarbonyl)piperidin-3-yl]ethoxy]-1-[3-[1-(t-butoxycarbonyl)piperidin-3-yl]propyl]-benzimidazoleYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (RS) 2-(4-chlorophenoxymethyl)-4-hydroxy-1-[3-[1-(t-butoxycarbonyl)piperidin-3-yl]propyl]benzimidazole (75 mg, 0.15 mmol, 1.0 eq) in dry N,N-dimethylformamide (1.0 ml) was treated with sodium hydride (60% in oil, 7.5 mg, 0.18 mmol, 1.20 eq). The resulting mixture was stirred at room temperature for thirty minutes, after which time 2-[1-(t-butoxycarbonyl)piperidin-3-yl]ethyl bromide (0.18 mmol, 1.2 eq) was added. The resulting mixture was stirred for three hours at 70° C. The reaction was quenched by the addition of water (10 ml). The aqueous fraction was extracted with diethyl ether (3×10 ml). The organic fractions were combined, washed with water (2×10 ml), then brine (1×10 ml), and then dried over sodium sulfate. The solvents were removed in vacuo to give a crude product. The title product was further purified by flash chromatography to provide a crystalline product. Yield: 92%

Workup

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

Sources & evidence

ORD record
ord-3f88a6870c6147d780e8eb52f51c4e0e
Source dataset
uspto-grants-2001_07
Patent number
US06255494B1

Reaction notes

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