Diisopropylethylamine → [5-Methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-methanol

HRID 251220Notes

Reaction equation

HRID 251220 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][NH:5][C:6]=1[CH2:7][OH:8].CCN(C(C)C)C(C)C.[CH3:18][Si:19]([CH3:26])([CH3:25])[CH2:20][CH2:21][O:22][CH2:23]Cl>CN(C=O)C.[Cl-].[Na+].O.O.CCOC(C)=O>[CH3:1][C:2]1[N:3]([CH2:23][O:22][CH2:21][CH2:20][Si:19]([CH3:26])([CH3:25])[CH3:18])[CH:4]=[N:5][C:6]=1[CH2:7][OH:8]

Participants

8

Reactant 3

HCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178433277HCID 178433277, compound

Product 1

HCID 67271606[5-Methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-methanolYield 56%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred solution of 4-methyl-5-imidazolemethanol (587 mg, 3.96 mmol) in anhydrous DMF (13 mL) was added DIPEA (2.1 mL, 11.9 mmol) followed by 2-(trimethylsilyl)ethoxymethyl chloride (793 mg, 4.76 mmol). The resultant solution was heated to 80° C. for 3 h then cooled to room temperature. The reaction mixture was poured into brine (15 mL), and diluted with H2O (6 mL) and EtOAc (40 mL). The phases were mixed vigorously for 10 minutes and separated. The organic phase was washed with brine (4×20 mL), dried (Na2SO4), and concentrated under reduced pressure. Purification of the crude orange oil by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 95:4:1) provided [5-Methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-methanol (535 mg, 56%) as a mixture of regioisomers.

Workup

  1. additionThe phases were mixed vigorously for 10 minutes
  2. customseparated
  3. washThe organic phase was washed with brine (4×20 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the crude orange oil by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 95:4:1)

Sources & evidence

ORD record
ord-51d4e3180cf246d09cad876904474b10
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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