Water → 2-[(1-naphthalen-1-ylmethyl-piperidin-4-ylmethyl)-(2-trimethylsilanyl-ethoxymethyl)-amino]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzimidazole-5-carboxylic acid methyl ester

HRID 2110023Notes

Reaction equation

HRID 2110023 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:32]=[CH:31][C:8]2[NH:9][C:10]([NH:12][CH2:13][CH:14]3[CH2:19][CH2:18][N:17]([CH2:20][C:21]4[C:30]5[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=5)[CH:24]=[CH:23][CH:22]=4)[CH2:16][CH2:15]3)=[N:11][C:7]=2[CH:6]=1)=[O:4].[H-].[Na+].[CH3:35][Si:36]([CH3:43])([CH3:42])[CH2:37][CH2:38][O:39][CH2:40]Cl.O.[O:45]1[CH2:49][CH2:48]C[CH2:46]1>>[CH3:1][O:2][C:3]([C:5]1[CH:32]=[CH:31][C:8]2[N:9]([CH2:46][O:45][CH2:49][CH2:48][Si:36]([CH3:42])([CH3:37])[CH3:35])[C:10]([N:12]([CH2:13][CH:14]3[CH2:19][CH2:18][N:17]([CH2:20][C:21]4[C:30]5[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=5)[CH:24]=[CH:23][CH:22]=4)[CH2:16][CH2:15]3)[CH2:40][O:39][CH2:38][CH2:37][Si:36]([CH3:43])([CH3:42])[CH3:35])=[N:11][C:7]=2[CH:6]=1)=[O:4]

Participants

6

Reactant 5

HCID 962WaterHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178497381HCID 178497381, compound

Product 1

HCID 690756512-[(1-naphthalen-1-ylmethyl-piperidin-4-ylmethyl)-(2-trimethylsilanyl-ethoxymethyl)-amino]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzimidazole-5-carboxylic acid methyl ester

Conditions

Temperature
0 °C

Procedure

After dissolving 2-[(1-naphthalen-1-ylmethyl-piperidin-4-ylmethyl)-amino]-1H-benzimidazole-5-carboxylic acid methyl ester (1 g, 2.33 mmol) in anhydrous tetrahydrofuran (30 ml) under a nitrogen stream, the mixture was cooled to 0° C. Next, 60% sodium hydride (187 mg, 4.89 mmol) was added and the mixture was stirred at 0° C. for 72 minutes. 2-(Trimethylsilyl)ethoxymethyl chloride (815.8 mg, 4.89 mmol) was further added, the mixture was stirred at 0° C. for 30 minutes, and then water was added. The solution was extracted with ethyl acetate and then with dichloromethane, and each extract was washed with saturated brine and then combined and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/3→3/2→1/0) to obtain 2-[(1-naphthalen-1-ylmethyl-piperidin-4-ylmethyl)-(2-trimethylsilanyl-ethoxymethyl)-amino]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzimidazole-5-carboxylic acid methyl ester. The compound was identified by LC-MS.

Workup

  1. stirringthe mixture was stirred at 0° C. for 30 minutes
  2. extractionThe solution was extracted with ethyl acetate
  3. washwith dichloromethane, and each extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/3→3/2→1/0)

Sources & evidence

ORD record
ord-604d11f7a2914157ba879391e51d54a3
Source dataset
uspto-grants-2009_04
Patent number
US07517875B2

Reaction notes

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