Diisopropylamine → Lithium diisopropylamide

HRID 256883Notes

Reaction equation

HRID 256883 reaction equation
C([Li:5])CCC.[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[CH3:13][N:14]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15]1.I[C:24]1[CH:29]=[N:28][CH:27]=[CH:26][N:25]=1>C1COCC1.CCCCCC.ClCCl.O>[CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[Li+:5].[CH3:13][N:14]1[CH2:18][CH2:17][C:16]([C:19]([O:21][CH3:22])=[O:20])([C:24]2[CH:29]=[N:28][CH:27]=[CH:26][N:25]=2)[CH2:15]1

Participants

10

Reactant 4

HCID 7912DiisopropylamineHCID 642841IodopyrazineHCID 13539132HCID 13539132, compoundHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 19784210HCID 19784210, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolvent

Procedure

A solution of lithium diisopropylamide in anhydrous THF was prepared by addition of n-butyllithium (7.9 ml of a 1.6M solution in hexane, 12.64 mmol) to a solution of diisopropylamine (1.4 g, 13.9 mmol) in THF (200 ml), at -78° C. The solution was stirred for 0.5 h before adding dropwise to a stirred solution of 1-methyl-3-carbomethoxypyrrolidine (1.5 g, 10.5 mmol) in THF (200 ml), at -78° C. After 1 h, a solution of 2-iodopyrazine (2.73 g, 13.3 mmol) in THF (10 ml) was added dropwise, at -78° C., stirred for 0.25 h, warmed to room temperature, and stirred for a further 16 h. Water (25 ml) and dichloromethane (150 ml) were added, stirred for 0.25 h before separating the aqueous and extracting into dichloromethane (3×100 ml). The combined extracts were dried (Na2SO4), concentrated under vacuum, and the residue purified by silica-gel chromatography using dichloromethane/methanol (92:8) as eluant. The title pyrazine was obtained as an orange oil (0.36 g) m/e 222 (M+); δ(360 MHz, CDCl3) 2.38 (3H, s, N--Me); 2.43-2.51 (1H, m, CH of CH2); 2.66-2.92 (3H, m, CH of CH2 and CH2 --N); 3.15 (1H, d, J=9.7 Hz, CH of CH2 --N) 3.33 (1H, d, J=9.7 Hz, CH of CH2 --N); 3.72 (3H, s, CO2Me); 8.44 (1H, d, J=1.5 Hz, pyrazine-H); 8.49 (1H, d, J=2 Hz, pyrazine-H), 8.64 (1H, dd, J=1.5 and 2 Hz, pyrazine-H).

Workup

  1. customat -78° C
  2. waitAfter 1 h
  3. stirringstirred for 0.25 h
  4. stirringstirred for a further 16 h
  5. stirringstirred for 0.25 h
  6. custombefore separating the aqueous and
  7. extractionextracting into dichloromethane (3×100 ml)
  8. dry with materialThe combined extracts were dried (Na2SO4)
  9. concentrationconcentrated under vacuum
  10. customthe residue purified by silica-gel chromatography

Sources & evidence

ORD record
ord-125e0dc8340c4a49b525428786fdbe3c
Source dataset
uspto-grants-1993_11
Patent number
US05260293

Reaction notes

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