Sodium hydride → HCID 59444124, compound

HRID 1968993Notes

Reaction equation

HRID 1968993 reaction equation
[C:1]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:10])[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[H-].[Na+].FC(F)(F)S(O[C:24]1[CH:29]=[CH:28][C:27]([CH2:30][O:31][CH3:32])=[CH:26][C:25]=1[N+:33]([O-:35])=[O:34])(=O)=O>CN(C=O)C>[CH3:32][O:31][CH2:30][C:27]1[CH:28]=[CH:29][C:24]([CH:2]([C:3]([O:5][C:6]([CH3:7])([CH3:8])[CH3:9])=[O:4])[C:1]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[C:25]([N+:33]([O-:35])=[O:34])[CH:26]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 68324Di-tert-butyl malonateHCID 59444104HCID 59444104, compound

Product 1

HCID 59444124HCID 59444124, compoundYield 55.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A stirred solution of bis(1,1-dimethylethyl) propanedioate (1.672 g, 7.73 mmol) in anhydrous DMF (25 mL) under argon was cooled to 0° C. and treated, portionwise with sodium hydride (0.297 g, 7.42 mmol) which was added over 10 mins. The resultant mixture was stirred at 0° C. for 15 mins and then allowed to warm to rt. After 1 hr the mixture was cooled back to 0° C. and treated with a solution of 4-[(methyloxy)methyl]-2-nitrophenyl trifluoromethanesulfonate D122 (1.95 g, 6.19 mmol) in DMF (5 mL) which was added slowly over 10 mins. After the addition was complete the cooling bath was removed and the mixture allowed to warm to rt. After 1 hr TLC indicated little or no reaction. The mixture was then warmed to 70° C. for 16 hr, then cooled to room temp and the solvent was removed under vacuum. The dark brown oily reside was dissolved in EtOAc (100 mL) and washed thoroughly with water (6×50 mL) and brine (50 mL), dried (MgSO4) and concentrated to dryness under vacuum. The residue was subjected to silica gel chromatography eluting with 0-5% MeOH in DCM to give the title compound as a yellow oil (1.32 g, 55.9%).

Workup

  1. additionwas added over 10 mins
  2. temperatureAfter 1 hr the mixture was cooled back to 0° C.
  3. additionwas added slowly over 10 mins
  4. additionAfter the addition
  5. customwas removed
  6. temperatureto warm to rt
  7. customno reaction
  8. temperatureThe mixture was then warmed to 70° C. for 16 hr
  9. temperaturecooled to room temp
  10. customthe solvent was removed under vacuum
  11. dissolutionThe dark brown oily reside was dissolved in EtOAc (100 mL)
  12. washwashed thoroughly with water (6×50 mL) and brine (50 mL)
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated to dryness under vacuum
  15. washeluting with 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-f7c50752df544ba389d43228007619b6
Source dataset
uspto-grants-2013_04
Patent number
US08426443B2

Reaction notes

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