Dimethylformamide → 4-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-2-carbaldehyde

HRID 251747Notes

Reaction equation

HRID 251747 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[N:11]=[CH:12][N:13]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li]CCCC.CN([CH:31]=[O:32])C>C1COCC1>[Si:1]([O:8][CH2:9][C:10]1[N:11]=[C:12]([CH:31]=[O:32])[N:13]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:20])([CH3:21])[CH3:22])[CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 220223854-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 575803574-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-2-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of 4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole (See WO03/022274) (1 eq) in THF at 40° C. was added dropwise a solution of BuLi (2 eq.) in hexanes and the mixture was stirred at 40° C. for a further 30 min. DMF (4 eq.) was then added and the cooling bath was removed and the reaction mixture was allowed to warm to RT and stirred for 30 min, after which time it was quenched by addition of a sat. aq. NH4Cl solution. The organics were extracted with EtOAc (2×), washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The material was purified by column chromatography on silica eluting with 15% EtOAc/petroleum ether. 1H NMR (300 MHz, CDCl3) δ: 9.81 (1H, s), 7.30 (1H, s), 5.95 (2H, s), 4.87, (2H, s), 3.58 (2H, t, J=7.7 Hz), 1.05-0.85 (20H, m), 0.05 (6H, s).

Workup

  1. customat 40° C.
  2. customthe cooling bath was removed
  3. temperatureto warm to RT
  4. stirringstirred for 30 min
  5. customafter which time it was quenched by addition of a sat. aq. NH4Cl solution
  6. extractionThe organics were extracted with EtOAc (2×)
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe material was purified by column chromatography on silica eluting with 15% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-783a28ba87394c4e8e20f7cfec405ea3
Source dataset
uspto-grants-2011_01
Patent number
US07863294B2

Reaction notes

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