Methyl iodide → 2H-3,1-Benzoxazine-2,4(1H)-dione, 6-chloro-1-methyl-

In a 3 L, 3 neck RBF equipped with mechanical stir, addition funnel, thermocouple and N2 inlet, NaH (30.4 g) was suspended in anhydrous THF (400 mL). While stirring at room temperature, a suspension of 5-chloroisatoic anhydride in THF (400 mL) was added in portion-wise manner over 45 min. The reaction mixture was stirred for 50 min (reaction temperature went up from 18 to 28° C.). To this was added CH3I (285 g, 125 mL) over 15 min. The mixture was then stirred at 42° C. for 16 h. Because TLC showed that some unreacted starting material was still present in the reaction mixture, an additional 30 mL of CH3I was added and the reaction mixture stirred at 42° C. for an additional 3 h. Reaction mixture was cooled (RT) and quenched by the slow (40 min) addition of AcOH (55 mL). Reaction mixture was concentrated to give 275 g thick syrupy product, which was used without any further purification. 1H NMR (300 MHz, CDCl3) δ 3.35 (s, 3H), 7.54 (d, 1H), 7.85 (d, 1H), 7.90 (s, 1H).

1. customIn a 3 L, 3 neck RBF equipped with mechanical stir, addition funnel
2. additionwas added in portion-wise manner over 45 min
3. stirringThe reaction mixture was stirred for 50 min (
4. customreaction temperature
5. customwent up from 18 to 28° C.
6. stirringThe mixture was then stirred at 42° C. for 16 h
7. stirringthe reaction mixture stirred at 42° C. for an additional 3 h
8. customReaction mixture
9. temperaturewas cooled (RT)
10. customquenched by the slow (40 min) addition of AcOH (55 mL)
11. customReaction mixture
12. concentrationwas concentrated

ORD record

ord-58eaaf9979e144f3be34af42f99506c0

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08673897B2