反应详情

To a stirred solution of 2-(4-acetyl-2-chlorophenyl)-2-methylpropanenitrile (1.57 g, 7.08 mmol) in 7 M ammonia in methanol solution (35 mL) is added freshly distilled titanium (IV) isopropoxide (4.2 mL, 14.2 mmol). The reaction mixture is left stirring 18 h at room temperature. After cooling to 0° C., sodium borohydride (0.40 g, 10.6 mmol) is added and the reaction mixture is stirred at 0° C. until no more gas evolved and then at room temperature for 4 h. Water (40 mL) is then added and the titanium oxide is removed by filtration on a Buchner funnel. The filtrate is extracted with EtOAc (3×50 mL) and the combined organic layers are concentrated under reduced pressure. The resulting residue is dissolved in Et2O (200 mL), washed with brine, dried over anhydrous MgSO4 and filtered. To this solution is then added 5 N HCl in 2-propanol (1.8 mL, 8.85 mmol). The resulting precipitate is filtered on a Buchner funnel and dried to provide the desired 2-(4-(1-aminoethyl)-2-chlorophenyl)-2-methylpropanenitrile hydrochloride (1.17 g, 64%) as a white solid. 1H NMR (300 MHz, CD3OD): δ 7.69 (1H, d, J=10.7 Hz), 7.68 (1H, s), 7.52 (1H, dd, J=8.3, 2.0 Hz), 4.53 (1H, q, J=6.8 Hz), 1.90 (6H, s), 1.66 (3H, d, J=6.9 Hz).

1. waitThe reaction mixture is left
2. temperatureAfter cooling to 0° C.
3. stirringthe reaction mixture is stirred at 0° C. until no more gas
4. waitat room temperature for 4 h
5. customthe titanium oxide is removed by filtration on a Buchner funnel
6. extractionThe filtrate is extracted with EtOAc (3×50 mL)
7. concentrationthe combined organic layers are concentrated under reduced pressure
8. dissolutionThe resulting residue is dissolved in Et2O (200 mL)
9. washwashed with brine
10. dry with materialdried over anhydrous MgSO4
11. filtrationfiltered
12. filtrationThe resulting precipitate is filtered on a Buchner funnel
13. customdried