反应详情

To LiAlH4 (1M in ether) (400 mL, 400 mmol) in a 2 L 3-neck flask with mechanical stirring under nitrogen at −5° C. was added concentrated H2SO4 (10.94 mL, 219 mmol) dropwise. Gas evolution was observed and the solution became cloudy and the foamy mixture was not as easy to stir. Temperature got as high as 3° C. The addition took 28 min. This mixture was stirred for 60 min and then the 3-bromo-4-methylbenzonitrile (37.3 g, 190 mmol) in THF (850 mL) was added over 18 min (max temp=10° C.). The slightly peach-colored mixture was stirred in the ice bath. After 30 min water (90 mL) was added carefully to give a white mixture, followed by 2M sodium hydroxide. After adding 100 mL, a solid that appeared to be amenable to filtration had formed. This was stirred for 30 min. The slightly waxy solid was filtered off and the single-phase filtrate washed with brine, dried and evaporated. This gave a slightly cloudy yellowish oil, 39.64 g (>100%) that was re-dissolved in ether (350 mL), filtered to remove some solid, and to the oil was added 1M hydrogen chloride in ether (1 eq based on starting nitrile, 190 mmol, 190 mL) slowly with stirring under nitrogen, This gave a solid that was collected by vacuum filtration and sucked dry, then dried under high vacuum to give 41.34 g (92%) of a white solid that the lab HPLC showed to be 98.8% pure with a retention time of 1.56 min. LC-MS m/z 200, 202 (M+H)+, 1.05 min (ret time).

1. customgot as high as 3° C
2. additionThe addition
3. stirringThis mixture was stirred for 60 min
4. customto give a white mixture
5. additionAfter adding 100 mL
6. filtrationto be amenable to filtration
7. customhad formed
8. stirringThis was stirred for 30 min
9. filtrationThe slightly waxy solid was filtered off
10. washthe single-phase filtrate washed with brine
11. customdried
12. customevaporated
13. customThis gave a slightly cloudy yellowish oil, 39.64 g (>100%) that
14. filtrationfiltered
15. customto remove some solid
16. stirringwith stirring under nitrogen
17. customThis gave a solid
18. filtrationthat was collected by vacuum filtration
19. customsucked dry
20. customdried under high vacuum