反应详情

A solution of intermediate 24, ethyl 2-(2-ethoxy-2-oxoethyl)-8,8-dimethyl-2,5,6,8-tetrahydro-[1,2,4]oxadiazolo[3,2-c][1,4]oxazine-2-carboxylate (31.16 g) in 1,2,4-trimethylbenzene (200 mL) was heated at 180° C. for 5 h. The resulting dark reaction solution was cooled then concentrated to give a dark brown paste which was taken up into ethyl acetate (250 mL) and extracted with 0.5 M aq Na2CO3 (4×50 mL). The organic layer was discarded and the aqueous layer acidified by carefully adding conc. HCl (20 mL) before being extracted with CH2Cl2 (4×50 mL). The combined CH2Cl2 layers were dried (Na2SO4), filtered and concentrated to give a dark paste which was dissolved in ether (100 mL) and allowed to stand at room temperature in a open flask. The brown/light yellow solid that formed was filtered to afford the title compound. The mother liquor that contained product was re-processed to afford additional material (combined yield ˜18–20% over two steps). 1H NMR (500 MHz, CDCl3) δ: 10.55 (1H, s), 4.45 (2H, q, J=7.0 Hz), 4.02 (4H, s), 1.61 (6H, s), 1.43 (3H, t, J=7.0 Hz). HRMS (M+H) calcd for C12H17N2O5: 269.1138; found: 269.1149. Anal calcd for C12H16N2O5: C, 53.72; H, 6.01; N, 10.44. Found: C, 53.71; H, 6.04; N, 10.30.

1. temperatureThe resulting dark reaction solution was cooled
2. concentrationthen concentrated
3. customto give a dark brown paste which
4. extractionextracted with 0.5 M aq Na2CO3 (4×50 mL)
5. extractionbefore being extracted with CH2Cl2 (4×50 mL)
6. dry with materialThe combined CH2Cl2 layers were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto give a dark paste which
10. customto stand at room temperature in a open flask
11. customThe brown/light yellow solid that formed
12. filtrationwas filtered