Diisopropylamine → HCID 21808099, compound

HRID 1852347Notes

Reaction equation

HRID 1852347 reaction equation
C([Li])[CH2:2][CH2:3][CH3:4].[CH:6](NC(C)C)([CH3:8])[CH3:7].C([NH:16]C(C)C)(C)C.[Li].[Li+].CC([N-]C(C)C)C.[C:29]([O:37]CC)(=O)[C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1.BrC(F)(F)C(F)(F)Br>C1COCC1.CC(C)=O.C1C=CC=CC=1.O>[CH:3]([C:34]1[C:35]([CH:6]([CH3:8])[CH3:7])=[C:30]([CH:31]=[CH:32][N:33]=1)[C:29]([NH2:16])=[O:37])([CH3:4])[CH3:2]

Participants

11

Reactant 6

HCID 7912DiisopropylamineHCID 15291Ethyl isonicotinate2×HCID 313011,2-Dibromo-1,1,2,2-tetrafluoroethaneHCID 2724682Lithium diisopropylamide2×HCID 45051747Lithium diisopropylamineHCID 178418339Butyllithium

Product 1

HCID 21808099HCID 21808099, compound

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 241BenzeneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (8.27 ml, 1.6 M in hexanes, 13.23 mmol) was added to diisopropylamine (13.36 mmol, 1.95 ml) in dry THF (10 ml) at −78° C. and stirred for 0.5 h (to make lithium diisopropylamine, LDA). The mixture was warmed to room temp. for 20 min, then cooled down to −78° C. again. Ethyl isonicotinate (1.00 g, 6.62 mmol, 0.91 ml) was dissolved in dry THF (30 mL) and cooled to −78° C. under an atmosphere of argon. The freshly prepared LDA was added to the ethyl isonicotinate solution dropwise. The mixture was left to stir for 1 h, then allowed to warm to room temperature for 0.5 h. The reaction mixture was cooled to −78° C. again and 1,2-dibromotetrafluoroethane (6.62 mmol, 0.79 ml) in THF (10 mL) was added slowly. The reaction was stirred at −78° C. for 1 h, then stirred at room temp. overnight. Water (40 ml) was added. The organic layer was separated, and the aqueous layer was washed with CHCl3 (3×100 ml). The combined organic solutions were dried (Na2SO4) and the solvent removed to give the crude compound. The crude compound was columned [8:2 benzene:acetone as eluant], to give diisopropyl isonicotinamide [Registry No. 77924-05-1]. 1H NMR (300 MHz, CDCl3) 8.66 (2H, d, J 6 Hz), 7.19 (2H, d, J 6 Hz), 3.69 (1H, bs), 3.55 (1H, bs), 1.54 (6H, bs) and 1.16 (6H, bs).

Workup

  1. temperatureThe mixture was warmed to room temp. for 20 min
  2. temperaturecooled to −78° C. under an atmosphere of argon
  3. waitThe mixture was left
  4. temperatureto warm to room temperature for 0.5 h
  5. temperatureThe reaction mixture was cooled to −78° C. again
  6. stirringThe reaction was stirred at −78° C. for 1 h
  7. stirringstirred at room temp. overnight
  8. customThe organic layer was separated
  9. washthe aqueous layer was washed with CHCl3 (3×100 ml)
  10. dry with materialThe combined organic solutions were dried (Na2SO4)
  11. customthe solvent removed
  12. customto give the crude compound

Sources & evidence

ORD record
ord-39b1cf04938145969a9fe2be94de585b
Source dataset
uspto-grants-2015_02
Patent number
US08962003B2

Reaction notes

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