Methyl iodide → (S)-tert-butyl 1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl(methyl)carbamate

HRID 416326Notes

Reaction equation

HRID 416326 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:11][CH:12]=[CH2:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:22]I.[H-].[Na+]>CN(C=O)C>[Si:1]([O:8][CH2:9][C@@H:10]([N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:11][CH:12]=[CH2:13])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 14153345(S)-tert-butyl 1-(tert-butyldimethylsilyloxy)pent-4-en-2-ylcarbamate

Product 1

HCID 57947449(S)-tert-butyl 1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl(methyl)carbamateYield 121.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-tert-butyl 1-(tert-butyldimethylsilyloxy)pent-4-en-2-ylcarbamate (95 g, 0.3 mol) and MeI (46.7 mL, 0.75 mol) in DMF (500 mL) was added sodium hydride (60%, 18 g, 0.45 mol) at 0° C. The reaction was stirred at 0° C. for 3 h and LC-MS showed the reaction was complete. 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 above steps were repeated with another 127 g of (S)-tert-butyl 1-(tert-butyldimethylsilyloxy)pent-4-en-2-ylcarbamate. The organic layers were combined and concentrated. The resulting residue was purified on silica gel column using a mixture of hexanes and EtOAc to give (S)-tert-butyl 1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl(methyl)carbamate (120 g, 40% for 4 steps). LRMS (M+H+) m/z 230.2.

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
  10. additiona mixture of hexanes and EtOAc

Sources & evidence

ORD record
ord-1c2760ef5e70413197f160c0148d22f7
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

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