Acrylonitrile → 3-(4-Methoxyphenoxy)propanenitrile

Temperature

80 °C

4-Methoxyphenol (263.0 g) was dissolved in acrylonitrile (224.8 g), and Triton B (18 mL) was added dropwise to the solution at room temperature, followed by stirring at 80° C. for 48 hours. The reaction mixture was cooled to room temperature under gentle stirring, and the mixture was further stirred for 12 hours. Subsequently, the mixture was left to stand at 6° C., to thereby allow precipitation of white prisms. After removal of the mother liquor through decantation, cold toluene (300 mL) was added, and crystals were collected through filtration. The thus-collected crude crystals were dried under reduced pressure at room temperature for 3 hours (crude crystals: 232.6 g). The crude crystals were dissolved in ethyl acetate (250 mL) at 50° C., and n-heptane (250 mL) was added slowly to the resultant solution under stirring. The crude crystals were recrystallized under gentle stirring for 12 hours. After removal of the mother liquor through decantation, n-heptane (300 mL) was added, and crystals were collected through filtration. The thus-collected crystals were washed with n-heptane (400 mL), and the crystals were dried under reduced pressure at room temperature (first crop of crystals: white prisms (154.5 g)). Since the mother liquor still produced crystals, they were collected as secondary crystals which were pale yellow prisms (second crop of crystals: pale yellow prisms (56.1 g)). Subsequently, all the filtrates and the n-heptane wash liquid were collected, and the combined mixture was concentrated under reduced pressure. Toluene (500 mL) was added to the residue, and the mixture was washed sequentially with 1N aqueous sodium hydroxide solution (100 mL×3), water (500 mL), 1N aqueous hydrochloric acid solution (100 mL×3), water (500 mL), and saturated brine (300 mL), followed by drying over sodium sulfate anhydrate for 30 minutes. After filtration, the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (150 mL) at 50° C., and n-heptane (150 mL) was slowly added to the resultant solution under stirring. The liquid was gently stirred for 12 hours for recrystallization. After removal of the mother liquor through decantation, n-heptane (200 mL) was added, and crystals were collected through filtration. The thus-collected crystals were washed with n-heptane (300 mL), followed by drying under reduced pressure at room temperature (third crop of crystals: white prisms (59.0 g)). In a similar manner, pale yellow prisms were collected as quaternary crystals (fourth crop of crystals: 19.0 g). The total amount of the four crystals was 288.6 g (yield: 76.9%), with crude crystals (yellow prisms) remaining (21.8 g, 5.8%).

1. additionTriton B (18 mL) was added dropwise to the solution at room temperature
2. temperatureThe reaction mixture was cooled to room temperature under gentle stirring
3. stirringthe mixture was further stirred for 12 hours
4. waitSubsequently, the mixture was left
5. customto stand at 6° C.
6. customprecipitation of white prisms
7. customAfter removal of the mother liquor through decantation, cold toluene (300 mL)
8. additionwas added
9. filtrationcrystals were collected through filtration
10. customThe thus-collected crude crystals
11. customwere dried under reduced pressure at room temperature for 3 hours (crude crystals
12. dissolutionThe crude crystals were dissolved in ethyl acetate (250 mL) at 50° C.
13. additionn-heptane (250 mL) was added slowly to the resultant solution
14. stirringunder stirring
15. customThe crude crystals were recrystallized
16. stirringunder gentle stirring for 12 hours
17. customAfter removal of the mother liquor through decantation, n-heptane (300 mL)
18. additionwas added
19. filtrationcrystals were collected through filtration
20. washThe thus-collected crystals were washed with n-heptane (400 mL)
21. dry with materialthe crystals were dried under reduced pressure at room temperature (first crop of crystals: white prisms (154.5 g))
22. customSince the mother liquor still produced crystals, they were collected as secondary crystals which
23. washSubsequently, all the filtrates and the n-heptane wash liquid
24. customwere collected
25. concentrationthe combined mixture was concentrated under reduced pressure
26. additionToluene (500 mL) was added to the residue
27. washthe mixture was washed sequentially with 1N aqueous sodium hydroxide solution (100 mL×3), water (500 mL), 1N aqueous hydrochloric acid solution (100 mL×3), water (500 mL), and saturated brine (300 mL)
28. dry with materialby drying over sodium sulfate anhydrate for 30 minutes
29. filtrationAfter filtration
30. concentrationthe filtrate was concentrated under reduced pressure
31. dissolutionThe residue was dissolved in ethyl acetate (150 mL) at 50° C.
32. additionn-heptane (150 mL) was slowly added to the resultant solution
33. stirringunder stirring
34. stirringThe liquid was gently stirred for 12 hours for recrystallization
35. customAfter removal of the mother liquor through decantation, n-heptane (200 mL)
36. additionwas added
37. filtrationcrystals were collected through filtration
38. washThe thus-collected crystals were washed with n-heptane (300 mL)
39. dry with materialby drying under reduced pressure at room temperature (third crop of crystals: white prisms (59.0 g))
40. customIn a similar manner, pale yellow prisms were collected as quaternary crystals (fourth crop of crystals: 19.0 g)

ORD record

ord-cab5e73ab1c440d98216ee3225be5216

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538242B2