反应详情

Phosgene in toluene (1.2M, 12.9 ml) is added to a mixture of 6-fluoro-1,2,3,4-tetrahydro-3,3-dimethylquinoxalin-2-one (IV, EXAMPLE 8, 1.001 g) and diisopropylethylamine (0.94 ml), and THF (10 ml) at 0°. After 45 min the reaction is allowed to warm to 20°-25°. After stirring for 3 hr, the reaction is again cooled to 0° and additional phosgene (4.2 ml) is added. The ice bath is removed and the reaction is stirred for 100 min, after which the excess phosgene and solvents are removed via a water aspirator. The mixture is then stirred with THF (10 ml) and of pyrrolidine (0.90 ml) are added. After stirring overnight, the reaction is concentrated mid the residue chromatographed on silica gel eluting with methanol/methylene chloride (2/98). The appropriate fractions are pooled and concentrated to give the title compound; MS (m/z) at 291; IR (mineral oil) 1681, 1660, 1396 and 1163 cm-1 ; NMR (CDCl3) 1.4-2.0, 3.15, 3.6, 6.43, 6.65, 6.76 and 8.32 δ.

1. temperatureto warm to 20°-25°
2. temperaturethe reaction is again cooled to 0°
3. customThe ice bath is removed
4. stirringthe reaction is stirred for 100 min
5. customafter which the excess phosgene and solvents are removed via a water aspirator
6. stirringThe mixture is then stirred with THF (10 ml) and of pyrrolidine (0.90 ml)
7. additionare added
8. stirringAfter stirring overnight
9. concentrationthe reaction is concentrated mid the residue
10. customchromatographed on silica gel eluting with methanol/methylene chloride (2/98)
11. concentrationconcentrated