Hydrochloric Acid → 2,3-DIHYDRO-4-TRICHLOROACETYLFURAN

Temperature

10 °C

To a nitrogen-purged, 5000-mL, three-neck, round-bottom flask equipped with a bottom stopcock, thermometer, mechanical stirrer, addition funnel and ice bath was charged 330.0 g (4.70 moles) of 2,3-dihydrofuran, 391 g (4.95 moles) of pyridine, and 1000 mL of n-heptane. The mixture was cooled to 10° C. then trichloroacetyl chloride (500 mL, 815 g, 4.48 moles) was added dropwise from the addition funnel. An ice bath was used to hold the reaction mixture at 11 to 220° C. during the 190 minute addition. The resulting yellow slurry was stirred at 22 to 28° C. for 45 minutes. To the mixture was added 700 mL of 10% aqueous HCl. After stirring to dissolve the solids, the lower (aqueous) layer was separated and discarded. The organic layer was washed sequentially with 500 mL of 10% HCl, 250 mL of 5% aqueous sodium bicarbonate and finally with 250 mL of water. The solution was placed in a 3000-mL, three-neck, round-bottom flask equipped with a magnetic stirrer, thermowell/thermocouple, heating mantle, and 12-inch Vigreux distillation head. The mixture was heated under vacuum (130 mm) to distill off the water/heptane azeotrope then most of the heptane. The mixture was distilled to a pot temperature of 102° C. (head temperature was 50° C.). A total of 1135 mL of distillate was collected. The resulting crude 2,3-dihydro-4-trichloroacetylfuran (881.38 g, theory 965.26 g) was 98.4% assay by nuclear magnetic resonance (NMR) (89.8% assay-yield). The crude product was used directly in the following example.

1. customTo a nitrogen-purged
2. custom5000-mL, three-neck, round-bottom flask equipped with a bottom stopcock
3. additionthermometer, mechanical stirrer, addition funnel and ice bath
4. customAn ice bath was used
5. customat 11 to 220° C.
6. additionduring the 190 minute addition
7. stirringAfter stirring
8. dissolutionto dissolve the solids
9. customthe lower (aqueous) layer was separated
10. washThe organic layer was washed sequentially with 500 mL of 10% HCl, 250 mL of 5% aqueous sodium bicarbonate and finally with 250 mL of water
11. customequipped with a magnetic stirrer
12. temperaturethermowell/thermocouple, heating mantle
13. distillation12-inch Vigreux distillation head
14. temperatureThe mixture was heated under vacuum (130 mm)
15. distillationto distill off the water/heptane
16. distillationThe mixture was distilled to a pot temperature of 102° C. (head temperature was 50° C.)
17. distillationA total of 1135 mL of distillate was collected
18. customby nuclear magnetic resonance (NMR) (89.8% assay-yield)

ORD record

ord-f6dc862745324829b8219c0ed603e33f

Source dataset

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06184394B2