Tetrahydrofuran → 1-Benzyl-4-[3-(1,1-dimethylethylamino)pyridyl]piperazine

HRID 2293774Notes

Reaction equation

HRID 2293774 reaction equation
C[Li].O1CCCC1.[CH2:8]([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[C:26]([NH:27][C:28]([C:31]#N)([CH3:30])[CH3:29])=[CH:25][CH:24]=[CH:23][N:22]=2)[CH2:17][CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(OCC)C>[CH2:8]([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[C:26]([NH:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:25][CH:24]=[CH:23][N:22]=2)[CH2:17][CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 540478341-Benzyl-4-[3-(1-cyano-1-methylethylamino)pyridyl]-piperazineHCID 178418348HCID 178418348, compound2×

Product 1

HCID 214776231-Benzyl-4-[3-(1,1-dimethylethylamino)pyridyl]piperazine

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Methyllithium (61 ml, 85 mmol) as a 1.4M solution in diethyl ether is added to 30 ml tetrahydrofuran and cooled to -78°. 1-Benzyl-4-[3-(1-cyano-1-methylethylamino)pyridyl]-piperazine (PREPARATION 95, 7.14 g, 21.28 mmol), dissolved in 30 ml cooled tetrahydrofuran, is cannulated into the methyllithium solution, rinsing in with 10 ml THF. The reaction is stirred at -78° and allowed to warm to 20°-25° overnight. The reaction is cautiously quenched with water, then extracted from water with methylene chloride. The extract is dried over sodium sulfate and concentrated. The concentrate is chromatographed on a 500 g silica gel column, eluting with ethyl acetate/hexane (2/3, v/v), the appropriate fractions are pooled and concentrated to give the title compound, NMR (300 MHz, CD3OD) 7.44, 7.43-7.07, 6.84-6.80, 3.49, 2.92, 2.52, 1.28 δ.

Workup

  1. temperaturecooled to -78°
  2. washrinsing in with 10 ml THF
  3. temperatureto warm to 20°-25° overnight
  4. customThe reaction is cautiously quenched with water
  5. extractionextracted from water with methylene chloride
  6. dry with materialThe extract is dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe concentrate is chromatographed on a 500 g silica gel column
  9. washeluting with ethyl acetate/hexane (2/3
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f353cc29d09d4d35b530fc1d885dc815
Source dataset
uspto-grants-1997_11
Patent number
US05686610

Reaction notes

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