Ammonium Chloride → [2-benzyloxymethyl-5-isopropyl-3-methyl-3H-imidazol-4-yl]-(3,5-dichlorophenyl)-methanol

HRID 1857733Notes

Reaction equation

HRID 1857733 reaction equation
[CH2:1]([O:8][CH2:9][C:10]1[NH:11][C:12](I)=[C:13]([CH:15]([CH3:17])[CH3:16])[N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19]([Li])CCC.[Cl:24][C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([Cl:33])[CH:32]=1)[CH:28]=[O:29].[Cl-].[NH4+]>O1CCCC1>[CH2:1]([O:8][CH2:9][C:10]1[N:11]([CH3:19])[C:12]([CH:28]([C:27]2[CH:26]=[C:25]([Cl:24])[CH:32]=[C:31]([Cl:33])[CH:30]=2)[OH:29])=[C:13]([CH:15]([CH3:17])[CH3:16])[N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 357463,5-DichlorobenzaldehydeHCID 178418339ButyllithiumHCID 1784401402-((benzyloxy)methyl)-4-iodo-5-isopropyl-1H-imidazole

Product 1

HCID 22130494[2-benzyloxymethyl-5-isopropyl-3-methyl-3H-imidazol-4-yl]-(3,5-dichlorophenyl)-methanolYield 33.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In 30 ml of dry tetrahydrofuran was dissolved 3.31 g (8.94 mmol) of 2-benzyloxymethyl-5-iodo-4-isopropyl-1-methylimidazole (4c), followed by addition of 5.78 ml (9.83 mmol) of n-butyllithium (1.70 M hexane solution) at -70° C. over 30 minutes. Then, after 5 minutes, a solution of 1.56 g (8.91 g) of 3,5-dichlorobenzaldehyde dissoloved in 10 ml of dry tetrahydrofuran was added at -70° C. over 30 minutes. After 1 hour, the mixture was left to cool to room temperature, and an aqueous solution of ammonium chloride was added thereto, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate/methylene chloride 10:1) to give 1.25 g of [2-benzyloxymethyl-5-isopropyl-3-methyl-3H-imidazol-4-yl]-(3,5-dichlorophenyl)-methanol (56) (yield 33.3%).

Workup

  1. additionwas added at -70° C. over 30 minutes
  2. waitAfter 1 hour
  3. waitthe mixture was left
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe crude product was purified by silica gel chromatography (ethyl acetate/methylene chloride 10:1)

Sources & evidence

ORD record
ord-f9b91a8c7888492fbd96ebdcbf6623d0
Source dataset
uspto-grants-2000_11
Patent number
US06147097

Reaction notes

Loading…