N-Iodosuccinimide → HCID 18783309, compound

Participants

Reaction Steps

According to the foregoing reaction scheme 1, 1-[[2-(trimethylsilyl)ethoxy]methyl]- imidazole (1) is treated with n-BuLi at -78° C. and reacted with phenyl disulfide to afford 1-[[2-(trimethylsilyl)ethoxy]methyl]-2-thiophenyl-imidazole (2). 1-[[2-(trimethylsilyl)ethoxy]methyl]-2-thiophenyl-imidazole (2) is oxidized with 2 equivalents of m-chloroperbenzoic acid to give 1-[[2-(trimethylsilyl)ethoxy]methyl]-2-sulfonylphenyl-imidazole (3). 1-[[2-(trimethylsilyl)ethoxy]methyl]-2-sulfonylphenyl-imidazole (3). is deprotonated with lithium diisopropylamide at -78° C. and treated with N-iodosuccinimide to afford 1-[[2-(trimethylsilyl)ethoxy]methyl]-2-sulfonylphenyl-5-iodo-imidazole (4). The corresponding grignard reagent of (4) is prepared by treatment with 1 equivalent of t-butyl magnesium chloride at 0° C. in anhydrous CH2Cl2 for 30 minutes and then reacted with 1,4-cyclohexanedione mono-ethylene ketal (5) to provide alcohol (6). The sulfonylphenyl protecting group is removed by treatment of (6) in methanol at 0° C. in the presence of 4 equivalents of sodium phosphate buffer with excess 2-3% Na(Hg) to give alcohol (7). Alcohol (7) is dehydrated by heating in THF/2 drops of water in the presence of a catalytic amount of PPTS to give olefin (8). The SEM protecting group is removed by treatment of (8) with n-butyl ammonium flouride at 60° C. to provide olefin (9). Catalytic hydrogenation of (9) over Pd(C) affords cyclohexane (10). Ketal deprotection of (10) proceeds smoothly with 5% HCl in THF at room temperature to give (1H -4(5)-imidazoyl)-4-cyclohexanone (11). The N-methoxy oxime is prepared by treatment of ketone (11) with N-methoxyl amine and TEA in dichloromethane to give (12). Finally, TBAH reduction of oxime (12) affords the (1H-(4,5)-imidazoyl)-4-cyclohexyl-N-methoxylamine (13). ##STR12##

Provenance & Evidence