反应详情

温度

80 °C

A sealable vial was charged with (4S,6S)-4-(5-bromo-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (4h, 585 mg, 1.647 mmol), sodium L-ascorbate (Acros; 32.6 mg, 0.165 mmol), sodium azide (Aldrich; 321 mg, 4.94 mmol), and copper(I) iodide (Aldrich; 94 mg, 0.494 mmol). The vial was evacuated and backfilled with Argon. EtOH (5.0 mL) and water (2.1 mL) were added, the reaction mixture purged with Argon, and then treated with N,N′-dimethyl-trans-1,2-cyclohexanediamine (Aldrich; 52.0 μL, 0.330 mmol). The reaction mixture was heated to 80° C. for 5 h and then stirred at ambient temperature for 16 h. A mixture of saturated aqueous NH4Cl and concentrated ammoniumhydroxide (5 mL; 9:1) was added, followed by EtOAc (10 mL). After 30 min, the reaction mixture was poured into a mixture of saturated aqueous NH4Cl/concentrated ammoniumhydroxide (50 mL; 9:1) and extracted with EtOAc (3×50 mL). The combined organic extracts were dried over Na2SO4 and concentrated to give a brown foam, which was dissolved in THF/water (8 mL; 3:1) and treated with trimethylphosphine (Aldrich; 1.0 M in THF) (2.0 mL, 2.000 mmol). The reaction mixture was stirred for 2 days and then concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (Gradient: 0%→10% MeOH/CH2Cl2) to give (4S,6S)-4-(5-amino-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (419 mg, 1.439 mmol) as a white foam. MS m/z=292.1 [M+H]+. Calculated for C12H13F4N3O: 291.2

1. customThe vial was evacuated
2. additionEtOH (5.0 mL) and water (2.1 mL) were added
3. customthe reaction mixture purged with Argon
4. additionwas added
5. waitAfter 30 min
6. extractionextracted with EtOAc (3×50 mL)
7. dry with materialThe combined organic extracts were dried over Na2SO4
8. concentrationconcentrated
9. customto give a brown foam, which
10. stirringThe reaction mixture was stirred for 2 days
11. concentrationconcentrated under reduced pressure
12. customThe crude product was purified by flash chromatography on silica gel (Gradient: 0%→10% MeOH/CH2Cl2)