Tetrahydrofuran → (1-(2-(fur-2-ylmethoxy)ethyl)-1H-benzimidazol-2-yl)(1-ethoxycarbonylpiperidin-4-yl)amine

HRID 582067Notes

Reaction equation

HRID 582067 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]1.O1CCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].CS([CH2:41][CH2:42][O:43][CH2:44][C:45]1[O:46][CH:47]=[CH:48][CH:49]=1)(=O)=O>O>[O:46]1[CH:47]=[CH:48][CH:49]=[C:45]1[CH2:44][O:43][CH2:42][CH2:41][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 30184551-Piperidinecarboxylic acid, 4-(1H-benzimidazol-2-ylamino)-, ethyl esterHCID 3251421Potassium bis(trimethylsilyl)amideHCID 21223641Fur-2-ylmethyl 2-methanesulfonylethyl ether

Product 1

HCID 53677515(1-(2-(fur-2-ylmethoxy)ethyl)-1H-benzimidazol-2-yl)(1-ethoxycarbonylpiperidin-4-yl)amine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-78 °C

Procedure

Combine (1H-benzimidazol-2-yl)(1-ethoxycarbonylpiperidin-4-yl)amine (0.5 g, 1.6 mmol) and tetrahydrofuran (10 mL). Cool to -78° C. Add dropwise, a solution of potassium bis(trimethylsilyl)amide (3.6 mL, 0.5M in toluene, 1.8 mmol). After 30 minutes, add fur-2-ylmethyl 2-methanesulfonylethyl ether (1.8 mmol). Warm to ambient temperature and heat to reflux. After 18 hours, cool to ambient temperature and add water. Separate the organic layer and extract the aqueous layer with dichloromethane. Dry the combined organic layers over Na2SO4, filter, and evaporate in vacuo to give (1-(2-(fur-2-ylmethoxy)ethyl)-1H-benzimidazol-2-yl)(1-ethoxycarbonylpiperidin-4-yl)amine: Rf =0.55 (2% triethylamine/10% methanol/ethyl acetate).

Workup

  1. additionAdd dropwise
  2. temperatureWarm to ambient temperature
  3. temperatureheat to reflux
  4. waitAfter 18 hours
  5. temperaturecool to ambient temperature
  6. customSeparate the organic layer
  7. extractionextract the aqueous layer with dichloromethane
  8. dry with materialDry the combined organic layers over Na2SO4
  9. filtrationfilter
  10. customevaporate in vacuo

Sources & evidence

ORD record
ord-d1ad043abaf94d33bf996d8fd1b7d3eb
Source dataset
uspto-grants-1999_07
Patent number
US05922737

Reaction notes

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