反应详情

A solution of 2.1 g (9.1 mmol) of 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylic acid Example 31) in 50 mL of methanol is cooled to 0° C. and saturated with hydrogen chloride gas. The reaction is stirred at room temperature for 18 hours, recooled to 0° C. and resaturated with hydrogen chloride gas. After stirring an additional 24 hours at room temperature, the solvent is removed in vacuo and the residue is partitioned between dichloromethane/5% aqueous sodium bicarbonate (200:100 mL). The organic layer is separated, washed with 5% aqueous sodium bicarbonate, water, dried (MgSO4), filtered, and concentrated in vacuo affording 1.9 g of the title compound. 1H NMR (400 MHz, CDCl3): 7.27 (bs, 1H), 7.24 (m, 1M), 4.26 (m, 1H), 3.82 (s, 3H), 3.75 (m, 1H), 3.62 (m, 1H), 1.22 (d, 3H).

1. customrecooled to 0° C.
2. stirringAfter stirring an additional 24 hours at room temperature
3. customthe solvent is removed in vacuo
4. customthe residue is partitioned between dichloromethane/5% aqueous sodium bicarbonate (200:100 mL)
5. customThe organic layer is separated
6. washwashed with 5% aqueous sodium bicarbonate, water
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo