反应详情

In a 10 L reactor, filled with nitrogen, about 100 mL of a solution of methallyl chloride (453 g, 490 mL, 5.0 moles) in dry tetrahydrofuran (THF) (4 L) is added to a stirred suspension of magnesium turnings (486 g, 20 moles) in THF (1 L), previously activated by 2 mL of methyl iodide. The mixture is heated until Grignard formation starts, then the reactor is cooled with ice and methallyl chloride solution is added at such a rate that the internal temperature does not exceed 50° C. After stirring overnight at room temperature, the Grignard is separated from the excess of magnesium, transferred to a 20 L reactor, and cooled to -40° C. A solution of fluoroacetonitrile (276 g, 253 mL, 4.68 moles) in THF (1 L) is added slowly (within about 15 min), maintaining the internal temperature between -40° and -35° C. Stirring is continued for 30 minutes at -40° C., then the mixture is cooled to -60° C. and hydrolyzed by slow addition of a water/THF mixture (300 mL, 1:1). After that, a solution of ammonium chloride (795 g) and sodium cyanide (490 g) in water (7.5 L), previously cooled with ice, is poured in rapidly, the dry ice bath is removed, and the mixture is stirred for 1 hour at an internal temperature between 0° C. and room temperature. After saturation with sodium chloride (about 2 kg), the organic layer is separated, and the aqueous phase is extracted twice with ether (2×3 L). Drying (Na2SO4) and evaporation gives a dark oil (687 g) which is dissolved in ether (5 L) and extracted carefully with 10% hydrochloric acid (4×650 mL). The combined aqueous phases are cooled with ice and made basic with conc. ammonia. The oil which separates is dissolved in diethyl ether (2.5 L), and the aqueous layer is extracted with diethyl ether (2×2 L). Drying (Na2SO4) and evaporation gives the crude title compound as a dark oil (488 g, 73%) which is used for the next step without further purification.

1. temperatureThe mixture is heated until Grignard formation starts
2. additionis added at such a rate that the internal temperature
3. customdoes not exceed 50° C
4. customthe Grignard is separated from the excess of magnesium
5. customtransferred to a 20 L reactor
6. temperaturecooled to -40° C
7. temperaturemaintaining the internal temperature between -40° and -35° C
8. stirringStirring
9. waitis continued for 30 minutes at -40° C.
10. customis removed
11. stirringthe mixture is stirred for 1 hour at an internal temperature between 0° C. and room temperature
12. customAfter saturation with sodium chloride (about 2 kg), the organic layer is separated
13. extractionthe aqueous phase is extracted twice with ether (2×3 L)
14. customDrying
15. custom(Na2SO4) and evaporation