Triisopropyl phosphite → 4-(4-Chlorophenyl)benzonitrile

온도

0 °C

A solution of 3.02 g (22.2 mmol) zinc chloride and 5.70 g (22.2 mmol) nickel acetylacetonate (moisture content<1%) in 165 mL of tetrahydrofuran was sequentially treated at room temperature with 0.40 mL (22.2 mmol) water, 10.9 mL (44.4 mmol) triisopropylphosphite, and 27.4 mL (44.4 mmol) of 1.62 M methylmagnesium chloride in tetrahydrofuran. The resultant clear, dark reddish solution was then treated with 111.0 g (609.8 mniol) 4-bromobenzonitrile and cooled to 0° C. The reaction mixture was treated with 653 mL (555 mmol) of 0.85 M 4-chlorophenylmagnesium bromide over a 75 minute period, keeping the temperature below 10° C. After the addition of the arylmagnesium reagent was complete, the reaction was stirred at 0° C. for an additional hour before quenching was carried out by adding 550 mL of 1 M aqueous sodium citrate solution. After adding 300 mL of methyl t-butyl ether (MTBE), the reaction mixture was stirred vigorously at room temperature for 1 h while air was bubbled through the solution. The contents of the reaction flask were transferred into a separatory funnel, and flask rinsed with an additional 250 mL of MTBE. The lower green aqueous phase was drained off and the clear yellow organic phase was washed twice with 100 mL of brine. The crude solid product left after concentration was dissolyed in 660 mL of chlorobenzene at 75° C., then 660 mL of heptane was added at a rate which maintained the temperature between 75-85° C. The clear yellow solution was then allowed to cool to ca. 40° C. and seeded with 1 mg of 4-(4'-chlorophenyl)benzonitrile. Crystallization commenced shortly after seeding, and the resultant slurry was cooled to 0-5° C. and stirred for 1 h. The solid product was filtered, washed with a small amount of heptane, and then dried under reduced pressure to afford 88.5 g (74.7%) of 4-(4'-chlorophenyl)benzonitrile as a fine white crystalline solid (m.p.=130.5-131.5° C.; identity confirmed by 1H- and 13C-NMR).

1. customthe temperature below 10° C
2. custombefore quenching
3. additionby adding 550 mL of 1 M aqueous sodium citrate solution
4. additionAfter adding 300 mL of methyl t-butyl ether (MTBE)
5. stirringthe reaction mixture was stirred vigorously at room temperature for 1 h while air
6. customwas bubbled through the solution
7. customThe contents of the reaction flask were transferred into a separatory funnel, and flask
8. washrinsed with an additional 250 mL of MTBE
9. washthe clear yellow organic phase was washed twice with 100 mL of brine
10. waitThe crude solid product left
11. concentrationafter concentration
12. customwas dissolyed in 660 mL of chlorobenzene at 75° C.
13. addition660 mL of heptane was added at a rate which
14. temperaturemaintained the temperature between 75-85° C
15. temperatureto cool to ca. 40° C.
16. customCrystallization
17. temperaturethe resultant slurry was cooled to 0-5° C.
18. stirringstirred for 1 h
19. filtrationThe solid product was filtered
20. washwashed with a small amount of heptane
21. customdried under reduced pressure

ORD 기록

ord-c9451c915a75433baf26235ad6ea9afb

출처 데이터셋

uspto-grants-1999_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05922898