Methyl iodide → HCID 18788444, compound

Participants

Reaction Steps

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.

Provenance & Evidence