反应详情

Methyl 4,5,6-trichloropicolinate (14.19 grams (g), 59.0 millimoles (mmol)) was slurried in 2-propanol (150 milliliters (mL)) in a 250 mL round bottom flask equipped with a Dean-Stark trap and a reflux condenser. Sulfuric acid (98% H2SO4; 8.07 g, 82 mmol) was added, and the reaction mixture was heated to reflux. After 20 hours (h) at reflux, the majority of the 2-propanol (100 mL) was distilled overhead. The pot solidified upon cooling to room temperature. The resulting solid was stirred with ethyl acetate (EtOAc; 500 mL) and saturated (satd) aqueous (aq) sodium bicarbonate solution (NaHCO3; 500 mL). The organic layer was separated, washed with brine and then filtered through Celite. The organic extract was concentrated to 150 mL by rotary evaporation. Hexane (100 mL) was added, and the solution was stored at −20° C. overnight. Crystals were collected, washed with hexane and dried in air (7.58 g, mp 104.6-105.7° C.). A second crop was obtained by concentration of the filtrate to give a total of 10.36 g (65%) 1H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H, pyridine H), 5.16 (septet, J=6.3 Hz, 1H, CHMe2), 1.34 (d, J=6.3 Hz, 6H, CHMe2); 13C{1H} NMR (101 MHz, CDCl3) δ 161.9 (CO2R), 150.6, 145.9, 145.0, 133.1, 125.4 (C3), 70.7 (CHMe2), 21.7 (Me). Anal. Calcd for C9H8Cl3NO2: C, 40.26; H, 3.00; N, 5.22. Found: C, 40.25; H, 3.02; N, 5.22.

1. customequipped with a Dean-Stark trap and a reflux condenser
2. temperaturethe reaction mixture was heated to reflux
3. temperatureAfter 20 hours (h) at reflux
4. distillationthe majority of the 2-propanol (100 mL) was distilled overhead
5. customThe organic layer was separated
6. washwashed with brine
7. filtrationfiltered through Celite
8. extractionThe organic extract
9. concentrationwas concentrated to 150 mL by rotary evaporation
10. additionHexane (100 mL) was added
11. customCrystals were collected
12. washwashed with hexane
13. customdried in air (7.58 g, mp 104.6-105.7° C.)
14. customA second crop was obtained by concentration of the filtrate
15. customto give a total of 10.36 g (65%) 1H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H, pyridine H), 5.16 (septet, J=6.3 Hz, 1H, CHMe2), 1.34 (d, J=6.3 Hz, 6H, CHMe2)