Sodium hydride → HCID 68484667, compound

HRID 1874985Notes

Reaction equation

HRID 1874985 reaction equation
[NH:1]1[CH:5]=[C:4]([CH:6]=O)[N:3]=[CH:2]1.[H-].[Na+].[CH3:10][Si:11]([CH2:14][CH2:15][O:16][CH2:17]Cl)([CH3:13])[CH3:12].N1C=CN=[C:20]1[CH:24]=O.[N:26]([CH2:29][C:30]([O-:32])=[O:31])=[N+]=[N-].[O-]CC.[Na+].[Cl-].[NH4+]>CN(C=O)C.C(O)C>[CH3:10][Si:11]([CH3:13])([CH3:12])[CH2:14][CH2:15][O:16][CH2:17][N:3]1[C:4]2[CH:6]=[C:29]([C:30]([O:32][CH2:20][CH3:24])=[O:31])[NH:26][C:5]=2[N:1]=[CH:2]1

Participants

10

Reactant 7

HCID 24758Sodium hydrideHCID 249551H-imidazole-2-carbaldehydeHCID 25517Ammonium ChlorideHCID 764281H-Imidazole-4-carbaldehydeHCID 2723922Sodium ethoxideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 57467870HCID 57467870, compound

Product 1

HCID 68484667HCID 68484667, compoundYield 45.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

1H-imidazole-4-carbaldehyde (1.05 g, 10.9 mmol) was added portion wise to a stirred suspension of NaH (0.437 g, 10.9 mmol) in 15 mL of DMF. After 1 hour a solution of SEM-Cl (1.93 mL, 10.9 mmol) in 3 mL of DMF was added dropwise over 10 minutes. The resulting solution was stirred for 3 hours at RT. The reaction mixture was partitioned between water and EtOAc. The organic layer was separated, dried over MgSO4 and evaporated to yellow oil. Purification was accomplished by silica gel column chromatography (40-100% EtOAc/hexanes) to afford the SEM protected imidazole carbaldehyde (1.8 g, 7.9 mmol) as a mixture of regioisomers. The mixture was dissolved in 5 mL of ethanol and azidoacetate (7.8 g, 15.1 mmol) was added. This solution was added to a solution of sodium ethoxide (8.91 mL, 23.86 mmol) at −20° C. After the addition was complete, the solution was stirred at −10° C. for 3 hours. The reaction mixture was poured into a saturated solution of ammonium chloride and extracted with ether 2×100 mL. The extracts were combined, dried over MgSO4, filtered and evaporated to an oil. Purification was accomplished by silica gel column chromatography (EtOAc/hexanes) to afford (1.111 g, 41% yield) of a yellow oil. The oil was dissolved in xylenes and heated to reflux for 3 hours. The solvent was evaporated under vacuum. Purification was accomplished by silica gel column chromatography (EtOAc/hexanes). The fractions collected contained multiple products and were combined. A second purification was accomplished by reverse-phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.088 g, 3%) as a solid. 1H NMR (400 MHz, CDCl3) δ ppm 10.80 (d, 1H), 8.77 (s, 1H), 6.97 (s, 1H), 5.71 (s, 2H), 4.38 (q, 2H), 3.41-3.84 (m, 2H), 1.39 (t, 3H), 0.83-1.11 (m, 2H), −0.03 (s, 9H).

Workup

  1. customThe reaction mixture was partitioned between water and EtOAc
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. customevaporated to yellow oil
  5. customPurification
  6. customto afford the SEM
  7. additionas a mixture of regioisomers
  8. additionAfter the addition
  9. stirringthe solution was stirred at −10° C. for 3 hours
  10. extractionextracted with ether 2×100 mL
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customevaporated to an oil
  14. customPurification

Sources & evidence

ORD record
ord-8a50a9ceb1af4f558f19ae4ce8d9b3c1
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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