Dimethylformamide → 1-[(Benzyloxy)methyl]-4-bromo-2-ethyl-5-formylimidazole

HRID 650265Notes

Reaction equation

HRID 650265 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[C:14](Br)=[C:13]([Br:16])[N:12]=[C:11]1[CH2:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.CCCCCC.CN([CH:33]=[O:34])C>C1COCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:14]([CH:33]=[O:34])=[C:13]([Br:16])[N:12]=[C:11]1[CH2:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8058HexaneHCID 186690441-[(Benzyloxy)methyl]4,5-dibromo-2-ethylimidazoleHCID 178418339Butyllithium

Product 1

HCID 186690401-[(Benzyloxy)methyl]-4-bromo-2-ethyl-5-formylimidazoleYield 93.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 1-[(Benzyloxy)methyl]-4,5-dibromo-2-ethylimidazole (28.0 g, 75.0 mmol, Part A of example 544) in THF (300 mL) was cooled to −78° C. under nitrogen atmosphere and then added dropwise 1.6 M n-BuLi in hexane (51.75 mL, 82.5 mmol, Aldrich) over 30 mins. The mixture was stirred at −78° C. for 30 mins and then added DMF (16.5 g, 225 mmol, Aldrich) dropwise over 15 mins. The mixture was stirred at −78° C. for 30 mins. A small portion of the reaction mixture was quenched with satd. NH4Cl at −78° C. TLC (30:70 EtOAc/hexane) revealed both starting material and product showed almost identical Rf values (0.71 & 0.70) along with another minor spot at Rf=0.15. However, mass spectrum (CI—NH3) revealed absence of starting material and formation of product (m/z=325, M+2H). The reaction mixture was quenched with satd. ammonium chloride (20 mL) at −78° C. and brought to room temp. The reaction mixture was extracted with ethyl acetate (3×100 mL), washed with brine and dried with anhydrous MgSO4. The solvent was evaporated under reduced pressure to afford crude yellow oil. The crude was purified by flah column chromatography on a silica gel using dichloromethane as eluent to afford 22.6 g (93%) of colorless oil. HRMS calcd. for C14H16N2O2Br: 323.0395. Found: 323.0394 (M+H).

Workup

  1. stirringThe mixture was stirred at −78° C. for 30 mins
  2. customA small portion of the reaction mixture was quenched with satd
  3. customat −78° C
  4. customThe reaction mixture was quenched with satd
  5. customat −78° C.
  6. custombrought to room temp
  7. extractionThe reaction mixture was extracted with ethyl acetate (3×100 mL)
  8. washwashed with brine
  9. dry with materialdried with anhydrous MgSO4
  10. customThe solvent was evaporated under reduced pressure
  11. customto afford crude yellow oil
  12. customThe crude was purified by flah column chromatography on a silica gel

Sources & evidence

ORD record
ord-a0ce560d376646b3857e666f8b42b68d
Source dataset
uspto-grants-2001_08
Patent number
US06271380B1

Reaction notes

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