反应详情

温度

30 °C

1-[(2'-(Triphenylmethyltetrazol-5-yl)biphenyl-4-yl)methyl]-2-butyl-4-chloro-5-hydroxymethylimidazole (920 g), and methanol (2.10 L) were charged to a 12-liter round-bottomed flask, equipped with mechanical stirrer, condenser with N2 inlet and thermometer. The slurry was cooled to ~10° C. and 3.4N hydrochloric acid (700 ml) was added over 10 minutes. After stirring two hours at 10°-20° C., the thick slurry was diluted with methanol (500 ml) and warmed to 30° C. After one hour at 30° C., the reaction was neutralized to pH 13 with 10N sodium hydroxide (420 ml). Solvent (largely methanol, 2.3 L) was distilled while 2.3 L D.I. water was added. Heating was discontinued and D.I. water (700 ml) and toluene (1.40 L) was added. After cooling to ~30° C., the organic phase was removed. The aqueous phase was reextracted with toluene (700 ml). Ethyl acetate (1.20 L) was added to the pot containing the aqueous phase. After stirring 10 minutes, acetic acid (130 ml) was added. The mixture was stirred one hour, then let stand overnight. Agitation was restarted and the slurry cooled to ~5° C. The product was isolated by vacuum filtration, reslurried with 1.50 L D.I. water and sucked semi-dry. The wet cake was charged to a 12 L round bottomed flask and reslurried 1/2 hour at ambient temperature with ethyl acetate (4.0 L). The product was isolated by vacuum filtration, washed with 200 ml ethyl acetate and dried in vacuo overnight at 50° C. Yield: 518 g, 88.5%. M.P.: 184°-185° C. Purity by HPLC: 98.8%.

1. customequipped with mechanical stirrer, condenser with N2 inlet
2. temperatureThe slurry was cooled to ~10° C.
3. waitAfter one hour at 30° C.
4. distillationSolvent (largely methanol, 2.3 L) was distilled while 2.3 L D.I
5. additionwater was added
6. temperatureHeating
7. additionwater (700 ml) and toluene (1.40 L) was added
8. temperatureAfter cooling to ~30° C.
9. customthe organic phase was removed
10. additionEthyl acetate (1.20 L) was added to the
11. additionpot containing the aqueous phase
12. stirringAfter stirring 10 minutes
13. additionacetic acid (130 ml) was added
14. stirringThe mixture was stirred one hour
15. waitlet stand overnight
16. temperaturethe slurry cooled to ~5° C
17. customThe product was isolated by vacuum filtration
18. additionThe wet cake was charged to a 12 L round bottomed flask
19. customThe product was isolated by vacuum filtration
20. washwashed with 200 ml ethyl acetate
21. customdried in vacuo overnight at 50° C