Diisopropylamine → Lithium diisopropylamide

HRID 1591316Notes

Reaction equation

HRID 1591316 reaction equation
C([Li:5])CCC.[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[CH3:13][C:14]1[CH:19]=[N:18][CH:17]=[CH:16][N:15]=1.[F:20][C:21]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:22]=1[C:23](OC)=[O:24].C(=O)(O)[O-].[Na+]>CCCCCC.O1CCCC1.O.C(O)(=O)C>[CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[Li+:5].[F:20][C:21]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:22]=1[C:23](=[O:24])[CH2:13][C:14]1[CH:19]=[N:18][CH:17]=[CH:16][N:15]=1

Participants

11

Reactant 5

HCID 7912DiisopropylamineHCID 79762-MethylpyrazineHCID 516892Sodium BicarbonateHCID 2782897Methyl 2,4-DifluorobenzoateHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 18956535HCID 18956535, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A solution of lithium diisopropylamide was prepared using n-butyllithium (20 ml of a 2.5M solution in hexane) and diisopropylamine (5.06 g) in dry tetrahydrofuran (100 ml) under an atmosphere of dry nitrogen as described in Example 1(i). To this solution at -70° was added 2-methylpyrazine (4.70 g) and the purple solution resulting was stirred at -70° for 0.5 hour. A solution of methyl 2,4-difluorobenzoate (8.60 g) in dry tetrahydrofuran (75 ml) was added over 0.5 hour and stirring was continued at -70° for a further 0.5 hour. Acetic acid (10 ml) was added and the temperature was allowed to rise to room temperature. The solution was diluted with water and the pH was adjusted to 7 with sodium bicarbonate. The mixture was extracted three times with ethyl acetate and the combined organic extracts were washed with water and dried (Na2SO4). The solvent was evaporated and the residue was chromatographed on silica gel. Elution with ethyl acetate/hexane (3:7) gave, after combination and evaporation of appropriate fractions, a solid which was crystallised from hexane to give the title compound, (5.90 g), m.p. 107°-108°.

Workup

  1. customthe purple solution resulting
  2. stirringstirring
  3. waitwas continued at -70° for a further 0.5 hour
  4. customto rise to room temperature
  5. extractionThe mixture was extracted three times with ethyl acetate
  6. washthe combined organic extracts were washed with water
  7. dry with materialdried (Na2SO4)
  8. customThe solvent was evaporated
  9. customthe residue was chromatographed on silica gel
  10. washElution with ethyl acetate/hexane (3:7)
  11. customgave
  12. customafter combination and evaporation of appropriate fractions
  13. customa solid which was crystallised from hexane

Sources & evidence

ORD record
ord-da3da2cb17c247e1aba3801bb0d3028f
Source dataset
uspto-grants-1993_04
Patent number
US05206364

Reaction notes

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