Sodium hydride → Methyl 2-((bis(tert-butoxycarbonyl)amino)methyl)-5-fluorobenzoate

HRID 1179323Notes

Reaction equation

HRID 1179323 reaction equation
[NH:1]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:2]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:3].[H-].[Na+].Br[CH2:19][C:20]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:21]=1[C:22]([O:24][CH3:25])=[O:23]>CN(C=O)C>[C:12]([O:11][C:9]([N:1]([CH2:19][C:20]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:21]=1[C:22]([O:24][CH3:25])=[O:23])[C:2]([O:4][C:5]([CH3:6])([CH3:7])[CH3:8])=[O:3])=[O:10])([CH3:15])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 279800Di-tert-butyl IminodicarboxylateHCID 15155455Methyl 2-(bromomethyl)-5-fluorobenzoate

Product 1

HCID 58978006Methyl 2-((bis(tert-butoxycarbonyl)amino)methyl)-5-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

In a dry flask under nitrogen, di-tert-butyl iminodicarboxylate (Aldrich, 3.86 g, 17.8 mmol) was dissolved in dry DMF (5 mL) and treated with NaH (60% dispersion in oil, 0.71 g, 17.8 mmol). After the evolution of gas had ceased, Methyl 2-(bromomethyl)-5-fluorobenzoate (4 g, 16.2 mmole) dissolved in DMF (5 mL) was added. An additional 5 mL of DMF was added to aid stirring. The reaction was stirred for 2 hrs, then partitioned between water and EtOAc. The organic layer was dried with Na2SO4, filtered and concentrated and the residue was purified on silica eluting first with toluene, then with a gradient of 0-5% MeOH/CHCl3. The impure product thus obtained was re-chromatographed on silica eluting with a gradient of 0-30% EtOAc/Hexanes. The product was obtained as a clear oil.

Workup

  1. additionwas added
  2. stirringThe reaction was stirred for 2 hrs
  3. custompartitioned between water and EtOAc
  4. dry with materialThe organic layer was dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified on silica eluting first with toluene
  8. customThe impure product thus obtained
  9. customwas re-chromatographed on silica eluting with a gradient of 0-30% EtOAc/Hexanes
  10. customThe product was obtained as a clear oil

Sources & evidence

ORD record
ord-0b25dbd5098a4c549699d8c19fc01d9f
Source dataset
uspto-grants-2007_10
Patent number
US07279487B2

Reaction notes

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