反应详情

温度

135 °C

[A1 is N, A2 is Cl—C, A3, A4 and A5 are CH, X is O and R1 isopropyl in the compound of formula I] Concentrated sulfuric acid (98% by weight, 510.2 g, 5.2 mol) is added to 2-chloro-6-trichloromethylpyridine (NP, 924 g, 4 mol) over a period of three hours at 135° C. The resulting mixture is stirred for three hours at 135° C. A viscous melted mass is obtained consisting of a mixture of intermediate IVa1 and Va1 with R1 being H and Hal being Cl, corresponding to an almost quantitative yield based on NP. The mass is added to isopropanol (2145 g) over a period of 30 minutes starting at ambient temperature which is raised to 60-65° C. Remaining isopropanol is removed by distillation under reduced pressure in three hours. The resulting product mixture is added to a mixture of xylene (1800 g) and water (1500 g). Upon heating to 50° C. the organic phase is separated and washed with water (1000 g). The obtained organic phase is dried and concentrated by distillation of xylene under reduced pressure (250 mbar). The resulting product (2070 g) contains 34.1 wt % of isopropyl 2-chloropyrid-6-ylcarboxylate in xylene which corresponds to a yield of 8.4% based on NP and is used for the preparation of N-4-fluorophenyl) 2-(3-trifluoromethylphenoxy)-pyrid-6-ylinecarboxamide without further purification (Examples 9 and 10).

1. customis obtained
2. additionconsisting of a mixture of intermediate IVa1 and Va1 with R1
3. customstarting at ambient temperature
4. temperatureis raised to 60-65° C
5. customRemaining isopropanol is removed by distillation under reduced pressure in three hours
6. additionThe resulting product mixture is added to a mixture of xylene (1800 g) and water (1500 g)
7. temperatureUpon heating to 50° C. the organic phase
8. customis separated
9. washwashed with water (1000 g)
10. customThe obtained organic phase is dried
11. concentrationconcentrated by distillation of xylene under reduced pressure (250 mbar)
12. customis used for the preparation of N-4-fluorophenyl) 2-(3-trifluoromethylphenoxy)-pyrid-6-ylinecarboxamide
13. customwithout further purification (Examples 9 and 10)