Diisopropylamine → N-[2,6-bis(1-methylethyl)phenyl]-5-(4-fluorophenyl)tetrahydro-2-oxo-3-furancarboxamide

HRID 2081616Notes

Reaction equation

HRID 2081616 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[O:25][C:23](=[O:24])[CH2:22][CH2:21]2)=[CH:16][CH:15]=1.[CH:26]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH:35]([CH3:37])[CH3:36])[C:30]=1[N:38]=[C:39]=[O:40])([CH3:28])[CH3:27]>CCOCC>[CH3:28][CH:26]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH:35]([CH3:36])[CH3:37])[C:30]=1[NH:38][C:39]([CH:22]1[CH2:21][CH:20]([C:17]2[CH:16]=[CH:15][C:14]([F:13])=[CH:19][CH:18]=2)[O:25][C:23]1=[O:24])=[O:40])[CH3:27]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 922592,6-Diisopropylphenyl isocyanateHCID 103541gamma-(4-Fluorophenyl)-gamma-butyrolactoneHCID 178418339Butyllithium

Product 1

HCID 19780277N-[2,6-bis(1-methylethyl)phenyl]-5-(4-fluorophenyl)tetrahydro-2-oxo-3-furancarboxamideYield 71.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent4×

Conditions

Temperature
-78 °C

Procedure

To a cooled (-78° C.) solution of diisopropylamine (1.40 g, 0.013 mol) in 90 mL ether, n-BuLi (0.013 mol) was added dropwise followed by 45 mL ether. After stirring for 5 minutes at -78° C. under a nitrogen atmosphere, a solution of γ-(4-fluorophenyl)-γ-butyrolactone (2.50 g, 0.013 mol) in 23 mL ether was added dropwise and the resulting solution was stirred for 20 minutes at -78° C. A solution of 2,6-diisopropylphenyl isocyanate in 23 mL ether was then added dropwise and the reaction mixture was allowed to gradually warm to room temperature and stir for 16 hours under a nitrogen atmosphere (J. F. Wolfe, et al, Synthetic Communications 17, 13 (1987)). The reaction mixture was then quenched with a saturated solution of ammonium chloride and extracted with methylene chloride. The layers were separated and the organic layer was washed two times with water, dried (Na2SO4) and concentrated in vacuo (30° C.) to afford a white residue. The residue was washed with hexane, filtered, and oven-dried (30° C.) to yield a white solid, 3.77 g (0.009 mol, 71.2%) of the title compound, mp 203°-205° C.

Workup

  1. additionwas added dropwise
  2. stirringthe resulting solution was stirred for 20 minutes at -78° C
  3. temperatureto gradually warm to room temperature
  4. stirringstir for 16 hours under a nitrogen atmosphere (J. F. Wolfe, et al, Synthetic Communications 17, 13 (1987))
  5. customThe reaction mixture was then quenched with a saturated solution of ammonium chloride
  6. extractionextracted with methylene chloride
  7. customThe layers were separated
  8. washthe organic layer was washed two times with water
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo (30° C.)
  11. customto afford a white residue
  12. washThe residue was washed with hexane
  13. filtrationfiltered
  14. customoven-dried (30° C.)

Sources & evidence

ORD record
ord-a37b82edf6464e8e92be633703070f74
Source dataset
uspto-grants-1993_02
Patent number
US05185349

Reaction notes

Loading…