反应详情

温度

0 °C

step 3—Sodium hydride (1.5 g of a 60% dispersion in mineral oil, 37.5 mmol) was suspended in DMF (50 mL) in a 250 mL round-bottom flask equipped with a stir bar, and cooled to 0° C. and maintained under a nitrogen atmosphere. A solution of 61a (4.6 g, 25 mmol) dissolved in DMF (50 mL) was added dropwise through a septum. The flask was removed from the ice bath and the mixture was stirred at RT for 30 m. The reaction was cooled to 10° C. and 1-bromomethyl-4-fluoro-benzene (3.74 mL, 30 mmol) was added through the septum. The flask was removed from the ice bath and the mixture was stirred at RT for 2 h. The reaction was poured into ice and 1N HCl, extracted twice with EtOAc, dried (Na2SO4), filtered and concentrated. A solid was precipitated from the EtOAc by addition of Et2O and hexanes to afford 3.0 g (41%) of 1-(4-fluoro-benzyl)-6-methyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione (61b): ms 2[M+Na]=605.

1. customequipped with a stir bar
2. temperaturemaintained under a nitrogen atmosphere
3. additionwas added dropwise through a septum
4. customThe flask was removed from the ice bath
5. temperatureThe reaction was cooled to 10° C.
6. customThe flask was removed from the ice bath
7. stirringthe mixture was stirred at RT for 2 h
8. additionThe reaction was poured into ice and 1N HCl
9. extractionextracted twice with EtOAc
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated
13. customA solid was precipitated from the EtOAc by addition of Et2O and hexanes