反应详情

5-Bromo-2-fluoropyridine (91) (0.52 mL, 5.05 mmol) was added to a solution of oxazine alcohol 134 (see Example 2BB) (500 mg, 2.51 mmol) in anhydrous DMF (10 mL) under N2 at 0° C. The resulting mixture was treated with 60% NaH (151 mg, 3.78 mmol), then quickly degassed and resealed under N2. Further 5-bromo-2-fluoropyridine (91) (0.52 mL, 5.05 mmol) was added and the mixture was stirred at room temperature for 2.5 h, and then cooled (CO2/acetone), quenched with ice/aqueous NaHCO3 (30 mL), added to brine (100 mL) and extracted with CH2Cl2 (8×100 mL). The combined extracts were evaporated to dryness and the residue was chromatographed on silica gel. Elution with 0-1% EtOAc/CH2Cl2 firstly gave foreruns, and then further elution with 2-4% EtOAc/CH2Cl2 gave 7-{[(5-bromo-2-pyridinyl)oxy]methyl}-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (136) (778 mg, 87%) as a white solid: mp (MeOH/CH2Cl2/hexane) 182-184° C.; 1H NMR [(CD3)2SO] δ 8.30 (dd, J=2.6, 0.5 Hz, 1H), 8.07 (s, 1H), 7.95 (dd, J=8.8, 2.6 Hz, 1H), 6.91 (dd, J=8.8, 0.6 Hz, 1H), 4.90 (m, 1H), 4.58 (dd, J=12.0, 3.3 Hz, 1H), 4.52 (dd, J=12.0, 6.0 Hz, 1H), 4.17 (ddd, J=12.6, 5.8, 2.8 Hz, 1H), 4.09 (ddd, J=12.5, 11.0, 5.2 Hz, 1H), 2.34-2.26 (m, 1H), 2.23-2.11 (m, 1H). Anal. (C12H11BrN4O4) C, H, N.

1. customquickly degassed
2. customquenched with ice/aqueous NaHCO3 (30 mL)
3. additionadded to brine (100 mL)
4. extractionextracted with CH2Cl2 (8×100 mL)
5. customThe combined extracts were evaporated to dryness
6. customthe residue was chromatographed on silica gel
7. washElution with 0-1% EtOAc/CH2Cl2 firstly gave foreruns
8. washfurther elution with 2-4% EtOAc/CH2Cl2