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

HRID 323180

Reaktionsgleichung

Reaktionsgleichung von HRID 323180
[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]

Komponenten

8

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 74236Tetrabutylammonium BromideKatalysatorHCID 962WaterLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

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, 0.5 M 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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-20895114483c47f899ae3cbfcfa8a476
Quelldatensatz
uspto-grants-2001_04
Patentnummer
US06211199B1

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