HCID 667570, compound → HCID 12044772, compound

HRID 379610Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][NH:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:29][Si:30]([CH3:37])([CH3:36])[CH2:31][CH2:32][O:33][CH2:34]Cl>CN(C=O)C.C1COCC1>[CH3:29][Si:30]([CH3:37])([CH3:36])[CH2:31][CH2:32][O:33][CH2:34][N:11]1[C:12]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[N:9]=[CH:10]1

Participants

Conditions

Temperature: -78 °C

Procedure

4-(4-Fluorophenyl)-5-(4-pyridyl)-1H-imidazole (3) (1 g 4.18 mmol) is dissolved in DMF/THF (50 ml/20 ml) and cooled to −78° C. Potassium bis-(trimethylsilyl)-amide (15% in toluene; 6.7 ml 5 mmol) is introduced at −78° C., stirred for 30 min. then 2-(trimethylsilyl)ethoxymethylchloride is added and the reaction mixture warmed up to r.t., poured on water after 2 hrs. and extracted 3× with ethyl acetate. The combined organic phases are dried over Na2SO4, evaporated to dryness and chromatographed (SiO2 acetone/hexane 4/6 to 6/4) to give 1-(2-(trimethylsilyl)ethoxymethyl)-4-(4-fluorophenyl)-5-(4-pyridyl)imidazole, being eluted first as white crystals (218 mg 14%) followed by 4-(4-pyridyl)-5-(4-fluorophenyl)-1-(2-(trimethylsilyl)ethoxymethyl) imidazole as white crystals (590 mg 38%). The correct assignment of the structures was achieved by ROESY, HSQC and HMBC spectrometry.

Workup

temperaturethe reaction mixture warmed up to r.t.
additionpoured on water after 2 hrs
extractionand extracted 3× with ethyl acetate
dry with materialThe combined organic phases are dried over Na2SO4
customevaporated to dryness
customchromatographed (SiO2 acetone/hexane 4/6 to 6/4)

Sources & evidence

ORD record: ord-92fe9d944845477f97a9ff1a2b4542b2
Source dataset: uspto-grants-2001_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06300347B1

Reaction notes

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