Methyl iodide → HCID 57947619, compound

HRID 341003Notes

Reaction equation

HRID 341003 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:18][O:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:10][C:11]([F:17])([F:16])[C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27]I.[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([CH3:27])[C@H:9]([CH2:18][O:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:10][C:11]([F:17])([F:16])[C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57947433HCID 57947433, compound

Product 1

HCID 57947619HCID 57947619, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of (S)-methyl 4-(tert-butoxycarbonylamino)-5-(tert-butoxycarbonyloxy)-2,2-difluoropentanoate (46.0 g, 0.12 mol) and MeI (15.0 mL, 0.24 mol) in DMF (300 mL) was added sodium hydride (60%, 7.2 g, 0.18 mol) at 0° C. The reaction mixture was stirred at 0° C. for 3 h and LC-MS showed the reaction was completed. The reaction was quenched with saturated NH4Cl solution and filtered. The filtrate was concentrated to remove most of DMF and the residue was dissolved in EtOAc (1.5 L). The organic layer was washed with water and brine, dried over Na2SO4. The organic layers were combined and concentrated. The resulting residue was purified on silica gel column (hexanes/EtOAc) to give (S)-methyl 4-(tert-butoxycarbonyl(methyl)amino)-5-(tert-butoxycarbonyloxy)-2,2-difluoropentanoate (42 g, 88%). LRMS (M+Na+) m/z 420.4.

Workup

  1. customThe reaction was quenched with saturated NH4Cl solution
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customto remove most of DMF
  5. dissolutionthe residue was dissolved in EtOAc (1.5 L)
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe resulting residue was purified on silica gel column (hexanes/EtOAc)

Sources & evidence

ORD record
ord-2cd1d5dfe08d4543b0416c49beb8c9d5
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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