反应详情

温度

50 °C

4-(2-Amino-2-methylpropyl)phenol (55.18 grams, 244.9 mmol) was added to 5.05 N KOH (97.2 mmol, 2.0 equiv). The mixture was warmed to 50° C. to give a homogeneous yellow solution. Chlorobenzene (1104 mL) and N,N-dimethylacetamide (10.7 grams, 122 mmol) were added and the mixture was heated to reflux (ca. 100° C.). The water was removed azeotropically via a Dean-Stark trap. At ca. 125° C. a solid began to form. When the pot temperature reached132° C. the water had been removed and the reaction mixture was a thick but stirrable slurry (mechanical stirring required). The Dean-Stark trap was removed and an additional 100 mL of chlorobenzene was removed and discarded. Dry chlorobenzene (50 mL) was added to the slurry, followed by ethyl 2-chloronicotinate (50.0 grams, 269 mmol) in chlorobenzene (50 mL). The slurry was heated at reflux until the reaction was complete (ca. 24, hours). As the reaction progressed the slurry thinned and became beige in color. After cooling to room temperature, water (385 mL) and 1 N NaOH (25 mL, 0.1 equiv) were added to the mixture and the phases were separated. The organic phase was washed with water (285 mL) and the solution was concentrated to a net weight of 700 grams (9.83% potency by HPLC, 89% yield) for use in the next reaction.

1. customto give a homogeneous yellow solution
2. temperaturethe mixture was heated
3. temperatureto reflux (ca. 100° C.)
4. customThe water was removed azeotropically via a Dean-Stark trap
5. customAt ca. 125° C.
6. customto form
7. customthe water had been removed
8. customThe Dean-Stark trap was removed
9. customan additional 100 mL of chlorobenzene was removed
10. additionDry chlorobenzene (50 mL) was added to the slurry
11. temperatureThe slurry was heated
12. temperatureat reflux until the reaction
13. temperatureAfter cooling to room temperature
14. customthe phases were separated
15. washThe organic phase was washed with water (285 mL)
16. concentrationthe solution was concentrated to a net weight of 700 grams (9.83% potency by HPLC, 89% yield) for use in the next reaction