反应详情

1-[(2'-(Trimethylstannyltetrazol-5-yl)-biphenyl-4-yl)methyl]-2-butyl-4-chloro-5-hydroxymethylimidazole (1.046 Kg), methylene chloride (5.00 L), tetrahydrofuran (0.85 L) and 10N sodium hydroxide (192 ml) were charged to a 12 liter round-bottomed flask equipped with mechanical stirrer, condenser with N2 inlet, and thermometer. After stirring five minutes at room temperature, triphenylmethyl chloride (0.530 Kg) was added and the mixture stirred three hours. 10N Sodium hydroxide (20 ml) and additional triphenylmethyl chloride (50 g) were added and the mixture stirred overnight. Deionized (D.I.) water (3.70 L) and 10N sodium hydroxide (30 ml) were added and the phases allowed to separate. The organic phase was washed twice with 2.0 L portions of water, dried with sodium sulfate (100 g) and filtered into a 12 L round-bottomed flask equipped for distillation. Methylene chloride (~2.0 L) was distilled. Heating was discontinued and heptane (5.0 L) was added. The resulting slurry was stirred at ambient temperature over the weekend (~68 hours). The mixture was cooled to ~5° C. and the product isolated by vacuum filtration, washed with heptane (1.0 L) and dried 48 hours in in vacuo at 40°-50° C. Yield: 959.5 g, 80%. M.P.: 167°-169° C. Purity by HPLC: 99.8%.

1. customequipped with mechanical stirrer, condenser with N2 inlet
2. stirringthe mixture stirred three hours
3. stirringthe mixture stirred overnight
4. customto separate
5. washThe organic phase was washed twice with 2.0 L portions of water
6. dry with materialdried with sodium sulfate (100 g)
7. filtrationfiltered into a 12 L round-bottomed flask
8. customequipped for distillation
9. distillationMethylene chloride (~2.0 L) was distilled
10. temperatureHeating
11. additionheptane (5.0 L) was added
12. stirringThe resulting slurry was stirred at ambient temperature over the weekend (~68 hours)
13. temperatureThe mixture was cooled to ~5° C.
14. customthe product isolated by vacuum filtration
15. washwashed with heptane (1.0 L)
16. customdried 48 hours in in vacuo at 40°-50° C