Tetrahydrofuran → (1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)(1-benzylpiperidin-4-yl)amine

HRID 582055

Reaction equation

HRID 582055 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]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:13][CH2:12]1.[O:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C(OCCCl)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(N(CC)CC)C.O>[CH2:25]([O:24][CH2:28][CH2:27][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]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:13][CH2:12]1)[CH3:26]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 12341Ethane, 1-chloro-2-ethoxy-2×HCID 3251421Potassium bis(trimethylsilyl)amideHCID 16640950N-(1-Benzylpiperidin-4-yl)-1H-benzimidazol-2-amine

Product 1

HCID 13808349(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)(1-benzylpiperidin-4-yl)amine

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-78 °C

Procedure

Combine (1H-benzimidazol-2-yl)(1-benzylpiperidin-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 2-chloroethyl ethyl ether (0.2 g, 1.8 mmol). Warm to ambient temperature and heat to reflux. After 4 hours, add 2-chloroethyl ethyl ether (0.2 g, 1.8 mmol) and tetrabutylammonium bromide (0.1 g). After 12 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 a residue. Chromatograph the residue on silica gel eluting with 2% triethylamine/10% methanol/ethyl acetate to give (1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)(1-benzylpiperidin-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 4 hours
  5. waitAfter 12 hours
  6. temperaturecool to ambient temperature
  7. customSeparate the organic layer
  8. extractionextract the aqueous layer with dichloromethane
  9. dry with materialDry the combined organic layers over Na2SO4
  10. filtrationfilter
  11. customevaporate in vacuo
  12. customto give a residue

Sources & evidence

ORD record
ord-dbdcc3a9aed748a691ebbdecc2115763
Source dataset
uspto-grants-1999_07
Patent number
US05922737

Linked notes

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