反应详情

温度

117.5 °C

A mixture of methyl 1-[(2′-cyanobiphenyl-4-yl)-methyl]-2-ethoxybenzimidazole-7-carboxylate [BEC] (228 kg) obtained in Reference Example 5, the residue containing trioctyltin azide [TOTA] obtained in Reference Example 6 and toluene (1148 L) was heated for about 40 hours under reflux (115-120° C.). The reaction solution was cooled and concentrated under reduced pressure. To the residue were added ethanol (764 kg) and sodium nitrite solution (135 kg/460 L) and the solution was adjusted to pH 4.5-5.5 with concentrated hydrochloric acid (about 224 kg). To the solution was added ethyl acetate (735 L) and the solution was adjusted to pH 0.5-1.5 with concentrated hydrochloric acid (about 100 L). To the solution was added hexane (1005 L) and the solution was adjusted to pH 3.5±0.5 with 4% sodium hydroxide solution. The solution was cooled to 10° C. or less and stirred for 1 hour. The crystals were separated and washed with a mixture of ethyl acetate (106 L) and hexane (310 L), followed by hexane (410 L) to give wet MET (396.6 kg).

1. customobtained in Reference Example 5
2. temperaturewas heated for about 40 hours
3. temperatureThe reaction solution was cooled
4. concentrationconcentrated under reduced pressure
5. additionTo the residue were added ethanol (764 kg) and sodium nitrite solution (135 kg/460 L)
6. additionTo the solution was added ethyl acetate (735 L)
7. additionTo the solution was added hexane (1005 L)
8. temperatureThe solution was cooled to 10° C. or less
9. customThe crystals were separated
10. washwashed with a mixture of ethyl acetate (106 L) and hexane (310 L)
11. customto give wet MET (396.6 kg)