反应详情

To a 200-mL RBF was added (s)-3-n-boc-amino piperidine (10.9 g, 54.4 mmol), Sodium bicarbonate (11.4 g, 136 mmol), THF, and 1-fluoro-2-nitro-4-(trifluoromethyl)benzene (7.62 ml, 54.4 mmol). The yellow mixture was heated to 70° C. with a water-cooled reflux condenser. The orange mixture was allowed to stir for 14 h, and was then cooled to ambient temperature, and filtered through a glass frit, rinsing with EtOAc. Concentration in vacuo afforded an orange oil, which crystallized on standing to an orange solid. The material was treated with 250 mL hexanes and heated on the rotovap (no vacuum) to 60° C. Small amounts of EtOAc were added until all solid dissolved, total volume of EtOAc was approx 10 mL. The solution was allowed to cool overnight, resulting in the formation of orange crystals. The liquid was decanted and the crystals rinsed twice with 50 mL hexanes. The crystals were collected to give (S)-tert-butyl 1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-ylcarbamate as orange crystals. The filtrate was concentrated to an orange solid. This material was treated with 150 mL hexanes and was heated to 65° C. Almost all of the material had dissolved. The hot liquid was decanted into a flask and allowed to cool overnight, resulting in an orange solid. The liquid was discarded, and additional crystals of (S)-tert-butyl 1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-ylcarbamate were collected. MS m/z=390 [M+H]+. Calc'd for C17H20F3N3: 389.

1. temperaturecooled
2. temperaturereflux condenser
3. filtrationfiltered through a glass frit
4. washrinsing with EtOAc
5. concentrationConcentration in vacuo
6. customafforded an orange oil, which
7. customcrystallized
8. additionThe material was treated with 250 mL hexanes
9. temperatureheated on the rotovap (no vacuum) to 60° C
10. additionSmall amounts of EtOAc were added until all solid
11. dissolutiondissolved
12. temperatureto cool overnight
13. customresulting in the formation of orange crystals
14. customThe liquid was decanted
15. washthe crystals rinsed twice with 50 mL hexanes
16. customThe crystals were collected