N-Iodosuccinimide → HCID 18783309, compound
Reaction equation
[CH3:1][Si:2]([CH3:22])([CH3:21])[CH2:3][CH2:4][O:5][CH2:6][C:7]1([C:16]2[NH:17][CH:18]=[CH:19][N:20]=2)[CH:12]=[CH:11][CH:10]=[CH:9][C:8]1=[S:13](=[O:15])=[O:14].C([N-]C(C)C)(C)C.[Li+].[I:31]N1C(=O)CCC1=O>>[CH3:1][Si:2]([CH3:22])([CH3:21])[CH2:3][CH2:4][O:5][CH2:6][C:7]1([C:16]2[NH:20][C:19]([I:31])=[CH:18][N:17]=2)[CH:12]=[CH:11][CH:10]=[CH:9][C:8]1=[S:13](=[O:15])=[O:14]Participants
Procedure
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##
Sources & evidence
- ORD record
- ord-fb24f8010737417ca5e49ecad79c417c
- Source dataset
- uspto-grants-2000_06
- Patent number
- US06072057
Reaction notes
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