Methyl iodide → HCID 18788444, compound

2,4-Dimethyl-2-methoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine 20 ml of 5% KOH are added to 11.3 mmol (2.5 g) of 2-ethoxycarbonyl-4-methyl-3,4-dihydro-2H-1,4-benzoxazine (described in J. Heterocyclic Chem., 1985, 22, 177) in 10 ml of ethanol and 10 ml of tetrahydrofuran. The reaction mixture is stirred at room temperature for 1 hour. The solvent is evaporated off, and the resulting residue is taken up in an ethyl acetate/water mixture, at acidic pH, and extracted. The organic phase is dried and concentrated. The residue is then dissolved in 90 ml of tetrahydrofuran and the temperature is reduced to -50° C. before the addition of 45.2 mmol (22.6 ml) of lithium diisopropylamide as a 2M solution in tetrahydrofuran. The reaction mixture is stirred for 2 hours at -50° C., and then 45.2 mmol (2.7 ml) of iodomethane are added and the temperature is brought back up to 25° C. in the course of 2 hours. After hydrolysis, the mixture is acidified to pH=4 and extracted with ethyl acetate. The organic phase is dried and concentrated. The residue is then dissolved in 150 ml of methanol in the presence of para-toluenesulphonic acid. The reaction mixture is heated at reflux for 18 hours. The solvent is evaporated off, and the mixture is taken up in an ethyl acetate/water mixture and extracted. The organic phase is dried, concentrated and purified by chromatography on silica gel using an ethyl acetate/petroleum ether mixture (3/7) as eluant to yield the expected compound.

1. customThe solvent is evaporated off
2. extractionextracted
3. customThe organic phase is dried
4. concentrationconcentrated
5. dissolutionThe residue is then dissolved in 90 ml of tetrahydrofuran
6. stirringThe reaction mixture is stirred for 2 hours at -50° C.
7. customis brought back up to 25° C. in the course of 2 hours
8. customAfter hydrolysis
9. extractionextracted with ethyl acetate
10. customThe organic phase is dried
11. concentrationconcentrated
12. dissolutionThe residue is then dissolved in 150 ml of methanol in the presence of para-toluenesulphonic acid
13. temperatureThe reaction mixture is heated
14. temperatureat reflux for 18 hours
15. customThe solvent is evaporated off
16. extractionextracted
17. customThe organic phase is dried
18. concentrationconcentrated
19. custompurified by chromatography on silica gel using an ethyl acetate/petroleum ether mixture (3/7) as eluant

ORD record

ord-936c522ca15a47bd8565581e7f604701

Source dataset

uspto-grants-2000_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06057317