Imidazole → HCID 178455504, compound

HRID 478842Notes

Reaction equation

HRID 478842 reaction equation
N1C=CN=C1.[Si:6](Cl)([C:19]([CH3:22])([CH3:21])[CH3:20])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[OH:24][CH2:25][C:26]1[CH:35]=[CH:34][C:29]2[N:30]=[C:31]([SH:33])[NH:32][C:28]=2[CH:27]=1.C(OC(C)C)(C)C>O.CO.CN(C=O)C>[Si:6]([O:24][CH2:25][C:26]1[CH:35]=[CH:34][C:29]2[N:30]=[C:31]([SH:33])[NH:32][C:28]=2[CH:27]=1)([C:19]([CH3:22])([CH3:21])[CH3:20])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 7914Diisopropyl EtherHCID 94078tert-ButyldiphenylchlorosilaneHCID 178519330HCID 178519330, compound

Product 1

HCID 178455504HCID 178455504, compoundYield 76.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Imidazole (24 g) and t-butyldiphenylsilyl chloride (96 g) were added to DMF (300 ml) solution of 5-hydroxymethyl-2-mercaptobenzoimidazole (60 g), and the mixture was stirred at room temperature for 2 hours. Next, this was mixed with MeOH (50 ml) and stirred and then mixed with water and diisopropyl ether and further stirred. The precipitate was collected by filtration and washed with water and diisopropyl ether to obtain 5-(t-butyldiphenylsilyloxymethyl)-2-mercaptobenzoimidazole (107 g). Next, 2-butanone (300 ml) solution of this compound (21 g) and ethyl 2-chloroacetoacetate (11 ml) was heated under reflux for 2 hours. The reaction mixture was concentrated under a reduced pressure, neutralized with saturated NaHCO3 aqueous solution and then extracted with EtOAc and washed with water and saturated brine. After drying with anhydrous MgSO4, the solvent was evaporated under a reduced pressure, and the resulting residue was purified by a silica gel column chromatography (to be referred to as column chromatography hereinafter) (eluent; n-hexane (to be referred to as Hex hereinafter):EtOAc=3:1-2:1), thereby obtaining ethyl 2-[(5-t-butyldiphenylsilyloxymethylbenzoimidazol-2-yl)thio]acetoacetate (23 g). Next, a DMF (300 ml) solution containing this compound, acetic acid formic acid anhydride (5.5 g) and Py (8.4 ml) was heated and stirred at 75° C. for 2 hours. The reaction mixture was concentrated under a reduced pressure while heating, diluted with EtOAc, washed with saturated NaHCO3 aqueous solution, water and saturated brine and then dried with anhydrous MgSO4, subsequently evaporating the solvent under a reduced pressure. The resulting residue was purified by a column chromatography (eluent; Hex:EtOAc=5:1-4:1) to obtain the title compound (16 g).

Workup

  1. stirringstirred
  2. filtrationThe precipitate was collected by filtration
  3. washwashed with water and diisopropyl ether

Sources & evidence

ORD record
ord-2c70bb67b6ad4c9dbc78f6ec69817c14
Source dataset
uspto-grants-2003_11
Patent number
US06642264B1

Reaction notes

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