1H-Imidazole-5-methanol, 4-methyl-, hydrochloride (1:1)

VERY SLIGHTLY BEIGE CRYSTALLINE POWDER

After the ammonia was collected, sodium (335 g., 15.23 m.) was added in portions and dissolved in the ammonia giving a deep blue solution. (5-Methyl-1H-imidazol-4-yl)methanol hydrochloride and (5-methyl-3H-imidazol-5-yl)methanol hydrochloride (5.00 g) were suspended in dichloromethane (100 mL), TEA (14.1 mL) and TBDPSCl (13.1 mL) were added under stirring, and stirring was continued for three days. The reaction mixture was diluted with water and extracted with chloroform. The combined extract liquid was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by flash chromatography (methanol/chloroform = 0% ' 5%) using a silica gel column (trade name: Cartridge 40M, manufactured by Biotage Ltd.) to give a mixture of the title compounds (7.77 g). 1H-NMR (CDCl3) delta: 1.05 (9H, s), 2.03 (3H, s), 4.68 (2H, s), 7.37-7.47 (7H, m), 7.66-7.68 (4H, m).(1) 4-(tert-Butyldiphenylsilyloxymethyl)-5-methyl-1H-imidazole, and 5-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1H-imidazole (5-Methyl-1H-imidazol-4-yl)methanol hydrochloride, and (4-methyl-1H-imidazol-5-yl)methanol hydrochloride (5.00 g) were suspended in dichloromethane (100 mL), followed by addition of triethylamine (14.1 mL) and TBDPSCl (13.1 mL) under stirring, and the stirring was continued for 3 days. The reaction solution was diluted with water, and extracted with chloroform. The combined extract was washed with saturated brine, dried over anhydrous sodium sulfate, and subsequently the solvent was distilled off under reduced pressure. The resulting residue was purified by flash chromatography (methanol/chloroform=0%?5%) using silica gel column (product name: cartridge 40M, manufactured by Biotage, Ltd.) to afford the mixture (7.77 g) of the title compound.1H-NMR (CDCl3) delta: 1.05 (9H, s), 2.03 (3H, s), 4.68 (2H, s), 7.37-7.47 (7H, m), 7.66-7.68 (4H, m).(1) 4-(tert-Butyldiphenylsilyloxymethyl)-5-methyl-1H-imidazole, and 5-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1H-imidazole (5-Methyl-1H-imidazol-4-yl)methanol hydrochloride, and (4-methyl-1H-imidazol-5-yl)methanol hydrochloride (5.00 g) were suspended in dichloromethane (100 mL), followed by addition of triethylamine (14.1 mL) and TBDPSCl (13.1 mL) under stirring, and the stirring was continued for 3 days. The reaction solution was diluted with water, and extracted with chloroform. The combined extract was washed with saturated brine, dried over anhydrous sodium sulfate, and subsequently the solvent was distilled off under reduced pressure. The resulting residue was purified by flash chromatography (methanol/chloroform=0%?5%) using silica gel column (product name: cartridge 40M, manufactured by Biotage, Ltd.) to afford the mixture (7.77 g) of the title compound.1H-NMR (CDCl3) delta: 1.05 (9H, s), 2.03 (3H, s), 4.68 (2H, s), 7.37-7.47 (7H, m), 7.66-7.68 (4H, m).(2) 4-(tert-Butyldiphenylsilyloxymethyl)-5-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole, and 5-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole The mixture (35.4 g) obtained in (1) was dissolved in acetonitrile (500 mL), followed by addition of TEA (37.8 mL) and then 2-trimethylsilylethoxymethyl chloride (hereinafter, also referred to as SEMCl) (21.4 mL) while stirring under ice cooling, followed by stirring at 70 C. for 12 hours. The reaction mixture was allowed to cool to room temperature, and the solvent was distilled off under reduced pressure. The residue was diluted with ethyl acetate, subsequently washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by flash chromatography (ethyl acetate/hexane=15%?50%) using silica gel column (product name: cartridge 65i, manufactured by Biotage, Ltd.) to afford 4-(tert-butyldiphenylsilyloxymethyl)-5-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole (17.9 g) as a low polar component, and 5-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole (9.42 g) as a high polar component.Low polar component: 4-(tert-butyldiphenylsilyloxymethyl)-5-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole1H-NMR (CDCl3) delta: -0.02 (9H, s), 0.89 (2H, t, J=8.2 Hz), 1.04 (9H, s), 2.10 (3H, s), 3.45 (2H, t, J=8.2 Hz), 4.65 (2H, s), 5.14 (2H, s), 7.34-7.45 (3H, m), 7.75-7.70 (4H, m).MS (ESI) m/z: 481 [M+H]+.High polar component: 5-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole1H-NMR (CDCl3) delta: -0.03 (9H, s), 0.89 (2H, t, J=8.0 Hz), 1.01 (9H, s), 1.92 (3H, s), 3.46 (2H, t, J=8.3 Hz), 4.68 (2H, s), 5.38 (2H, s), 7.37-7.47 (3H, m), 7.66-7.68 (4H, m).MS (ESI) m/z: 481 [M+H]+.

Molecular Weight:148.59
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:148.0403406
Monoisotopic Mass:148.0403406
Topological Polar Surface Area:48.9
Heavy Atom Count:9
Complexity:76.8
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes