3-sulfanylpropane-1,2-diol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Mercapto-1,2-propanediol(3.26 g, 30.00 mmol) was dissolved in benzene (60 mL). Benzophenone dimethyl ketal (13.48 g, 60.0 mmol, 2 equiv.) and CSA (0.70 mg, 3.00 mmol, 0.1 equiv.) were added. The solution was heated with an oil bath to reflux. Benzene/methanol was collected and removed while more benzene was added to the refluxing reaction. After about 200 mL benzene/methanol was distilled out, the reaction was cooled to room temperature, applied directly onto a silica gel column. The column was then eluted was 20%-40% ether/petroleum ether to afford a thick oil as the desired product (3.78 g, 46). Rf=0.25, 20% ether/petroleum ether. 1H NMR (400 MHz, C6D6) δ=2.56 (dd, J=6.3, 10.2 Hz, 1 H), 2.83 (dd, J=7.7, 10.2 Hz, 1 H), 3.35 (br dd, J=5.3, 11.6 Hz, 1 H), 3.44 (br dd, J=3.5, 11.6 Hz, 1 H), 3.88-3.95 (m, 1 H), 6.94-7.20 (m, 6H), 7.54 (d, J=7.5 Hz, 2 H), 7.70 (d, J=7.5 Hz, 2 H). 13C NMR (100 MHz, C6D6) δ=35.90, 63.97, 83.29, 100.20, 126-129 (m). The solution was heated with an oil bath to reflux Benzene/methanol was collected removed while more benzene was added to the refluxing reaction After about 200 mL benzene/methanol was distilled out The column was then eluted

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-mercapto-1,2-propanediol (5.00 g, 46.23 mmol) and imidazole (3.78 g, 55.47 mmol) in dimethylformamide (30 mL) was added t-butyldiphenylsilyl chloride (12.71 g, 46.23 mmol) at room temperature. After stirring for 18 h the reaction was quenched by the addition of saturated sodium bicarbonate and the mixture was extracted with ether (3X). The combined ether extracts were washed with water (2X), brine, dried and concentrated to give a yellow oil. The crude material was purified by flash chromatography with a mixture of hexanes and ethyl acetate (90:10) to give the compound as a colorless oil (14.12 g) in 88% yield. was quenched by the addition of saturated sodium bicarbonate the mixture was extracted with ether (3X) The combined ether extracts were washed with water (2X), brine dried concentrated to give a yellow oil The crude material was purified by flash chromatography with a mixture of hexanes and ethyl acetate (90:10)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Mercapto-1,2-propanediol(3.26 g, 30.00 mmol) was dissolved in benzene (60 mL). Benzophenone dimethyl ketal (13.48 g, 60.0 mmol, 2 equiv.) and CSA (0.70 mg, 3.00 mmol, 0.1 equiv.) were added. The solution was heated with an oil bath to reflux. Benzene/methanol was collected and removed while more benzene was added to the refluxing reaction. After about 200 mL benzene/methanol was distilled out, the reaction was cooled to room temperature, applied directly onto a silica gel column. The column was then eluted was 20%-40% ether/petroleum ether to afford a thick oil as the desired product (3.78 g, 46). Rf =0.25, 20% ether/petroleum ether. 1H NMR (400 MHz, C6D6) δ=2.56 (dd, J=6.3, 10.2 Hz, 1H), 2.83 (dd, J=7.7, 10.2 Hz, 1H), 3.35 (br dd, J=5.3, 11.6 Hz, 1H), 3.44 (br dd, J=3.5, 11.6 Hz, 1H), 3.88-3.95 (m, 1H), 6.94-7.20 (m, 6H), 7.54 (d, J=7.5 Hz, 2H), 7.70 (d, J=7.5 Hz, 2H). 13C NMR (100 MHz, C6D6) δ=35.90, 63.97, 83.29, 100.20, 126-129 (m). The solution was heated with an oil bath to reflux Benzene/methanol was collected removed while more benzene was added to the refluxing reaction After about 200 mL benzene/methanol was distilled out The column was then eluted

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-[2-(1-Oxo-2,2,2-trifluoroethyl)-1H-pyrrol-1-yl]-2-propyl-1-[(2'-(1H-tetrazol-5-yl)biphen-4-yl)methyl]-1H-imidazole-5-carboxylate (2.5 g) from Example 13 was dissolved in DMF (45 mL). Water (0.4 mL) followed by potassium carbonate (3.1 g) were added and the reaction mixture stirred at room temperature for 48 hours. Tlc of the reaction mixture showed the reaction to be incomplete. Additional potassium carbonate (0.6 g) and water (0.2 mL) were added and the reaction mixture stirred at room temperature for an another 18 hours. The insoluble materials were removed from the reaction mixture by filtration and washed with DMF A 10% citric acid solution (100 mL) was added slowly to the filtrate and the resulting mixture extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and the solvent removed under reduced pressure. The residue was recrystallized from hexane/ethyl acetate to afford 2.06 g (85% yield) of the title compound, mp 185°-188° C., MS (FAB, thioglycerol) 550.3 (M+1). were added the reaction the reaction mixture stirred at room temperature for an another 18 hours The insoluble materials were removed from the reaction mixture by filtration washed with DMF A 10% citric acid solution (100 mL) was added slowly to the filtrate the resulting mixture extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate the solvent removed under reduced pressure The residue was recrystallized from hexane/ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-[2-(1-Oxo-2,2,2-trifluoroethyl)-1H-pyrrol-1-yl]-2-propyl-1-[(2'-(1H-tetrazol-5-yl)biphen-4-yl)methyl]-1H-imidazole-5-carboxylate (2.5 g) from Example 13 was dissolved in DMF (45 mL). Water (0.4 mL) followed by potassium carbonate (3.1 g) were added and the reaction mixture stirred at room temperature for 48 hours. Tlc of the reaction mixture showed the reaction to be incomplete. Additional potassium carbonate (0.6 g) and water (0.2 mL) were added and the reaction mixture stirred at room temperature for an another 18 hours. The insoluble materials were removed from the reaction mixture by filtration and washed with DMF A 10% citric acid solution (100 mL) was added slowly to the filtrate and the resulting mixture extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and the solvent removed under reduced pressure. The residue was recrystallized from hexane/ethyl acetate to afford 2.06 g (85% yield) of the title compound, mp 185°-188° C., MS (FAB, thioglycerol) 550.3 (M+1). were added the reaction the reaction mixture stirred at room temperature for an another 18 hours The insoluble materials were removed from the reaction mixture by filtration washed with DMF A 10% citric acid solution (100 mL) was added slowly to the filtrate the resulting mixture extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate the solvent removed under reduced pressure The residue was recrystallized from hexane/ethyl acetate