反应详情

To a stirred solution of 2-(4-acetyl-2-methylphenyl)-2-methylpropanenitrile (1.77 g, 8.80 mmol) in 7 M ammonia in MeOH (45 mL) is added freshly distilled titanium (IV) isopropoxide (5.20 mL, 17.6 mmol). The reaction mixture is left stirring 18 h at room temperature. After cooling to 0° C., sodium borohydride (500 mg, 13.2 mmol) is added and the reaction mixture stirred at 0° C. until no more gas evolved and then at room temperature 3 h. Water (25 mL) is then added and the titanium oxide removed by filtration on a Buchner funnel. The filtrate is extracted with EtOAc (3×100 mL) (brine (10 mL) is added to help separation between both layers) and the combined organic layers are concentrated under reduced pressure. The resulting crude product (which contained water) is dissolved in Et2O (75 mL), washed with brine, dried over MgSO4 and filtered. 5-6 N HCl in 2-propanol (2.2 mL) is slowly added to the well-stirred filtrate. The resulting white precipitate is filtered on a Buchner funnel and dried in vacuo to provide the expected product 2-[4-(1-aminoethyl)-2-methylphenyl]-2-methylpropanenitrile (1.58 g, 75%) as a white solid. 1H NMR (300 MHz, CD3OD): δ 7.55 (1H, d, J=8.0 Hz), 7.44-7.37 (2H, m), 4.97 (3H, s), 4.52 (1H, q, J=6.9 Hz), 2.75 (3H, s), 1.86 (6H, s), 1.69 (3H, d, J=6.9 Hz).

1. waitThe reaction mixture is left
2. temperatureAfter cooling to 0° C.
3. stirringthe reaction mixture stirred at 0° C. until no more gas
4. customat room temperature
5. custom3 h
6. customthe titanium oxide removed by filtration on a Buchner funnel
7. extractionThe filtrate is extracted with EtOAc (3×100 mL) (brine (10 mL)
8. additionis added
9. customseparation between both layers) and the combined organic layers
10. concentrationare concentrated under reduced pressure
11. dissolutionThe resulting crude product (which contained water) is dissolved in Et2O (75 mL)
12. washwashed with brine
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. addition5-6 N HCl in 2-propanol (2.2 mL) is slowly added to the well-stirred filtrate
16. filtrationThe resulting white precipitate is filtered on a Buchner funnel
17. customdried in vacuo