反应详情

温度

0 °C

To a solution of trans-4-(2-chloro-5-trifluoromethyl-benzoylamino)-cyclohexane carboxylic acid methyl ester (step 1) (95.2 g, 0.26 mol) in dry THF (1 L) under nitrogen at 0° C. is added lithium aluminium hydride pellets (20 g, 0.53 mol) portion wise over 3 hours. The reaction mixture is stirred at 0° C. for a further 2 hours and then carefully quenched at 0° C. by the addition of water (40 mL) in THF (60 mL) followed by further THF (500 mL) to maintain a mobile suspension. Finally, 1M sodium hydroxide solution (80 mL) is added at 0° C. resulting in a yellow solution containing a colourless suspension. The reaction is filtered through a Celite® pad (filter material) to remove inorganic salts. The Celite® pad/salts are washed with EtOAc (500 mL) then with EtOAc:THF (1:1; 300 mL). The organics are combined and diluted with further EtOAc (600 mL) and then washed with saturated brine (600 mL). The organic layer is dried (Na2SO4), filtered and concentrated under reduced pressure until a slurry is obtained. Et2O is added to the slurry, which is then stirred for 5 minutes before being filtered to recover a colourless solid. The solid is washed with isohexane and then dried at 35° C. under vacuum to give the required product.

1. customcarefully quenched at 0° C. by the addition of water (40 mL) in THF (60 mL)
2. temperatureto maintain a mobile suspension
3. additionFinally, 1M sodium hydroxide solution (80 mL) is added at 0° C.
4. customresulting in a yellow solution
5. additioncontaining a colourless suspension
6. filtrationThe reaction is filtered through a Celite® pad (filter material)
7. customto remove inorganic salts
8. washThe Celite® pad/salts are washed with EtOAc (500 mL)
9. additiondiluted with further EtOAc (600 mL)
10. washwashed with saturated brine (600 mL)
11. dry with materialThe organic layer is dried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure until a slurry
14. customis obtained
15. stirringis then stirred for 5 minutes
16. filtrationbefore being filtered
17. customto recover a colourless solid
18. washThe solid is washed with isohexane
19. customdried at 35° C. under vacuum