Sodium Bicarbonate → 7,8-Difluoro-2,3-dihydro-3-methyl-4H-(1,4)benzoxazine

To the ethyl acetate layer were added 0.47 g of sodium borohydride and 2 ml of ethanol, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was washed twice with 10 ml portions of 5% aqueous citric acid solution and once with 10 ml of dilute aqueous ammonia (the same as mentioned hereinbefore), and dried over anhydrous magnesium sulfate. The desiccant was filtered off and to the solution was added with 0.72 ml of concentrated hydrochloric acid with stirring. After cooling with ice-water, the resulting crystals were collected by filtration and washed with cold ethyl acetate to give 1.236 g of 7,8-difluoro-3-methyl-3,4-dihydro-2H-[1,4]benzoxazine hydrochloride as colorless crystals. Optical purity: 1.0% e.e., (S), 3S:3R =1.02:1.00. In 10 ml of chloroform was suspended 1.078 g of the above hydrochloride and to the suspension was added 10 ml of 5% aqueous sodium hydrogen carbonate solution with stirring. The chloroform layer was washed with water and dried over anhydrous magnesium sulfate. Then, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The residue was dissolved in 1 ml of methanol, followed by addition of 5 ml of 50% aqueous methanol. After cooling with ice-water, the resulting crystals were collected by filtration to give 0.596 g of the title compound (yield: 60.9%).

1. washThe chloroform layer was washed with water
2. dry with materialdried over anhydrous magnesium sulfate
3. filtrationThen, the desiccant was filtered off
4. distillationthe solvent was distilled off under reduced pressure
5. dissolutionThe residue was dissolved in 1 ml of methanol
6. additionfollowed by addition of 5 ml of 50% aqueous methanol
7. temperatureAfter cooling with ice-water
8. filtrationthe resulting crystals were collected by filtration

ORD record

ord-d5b2dc789ae74fdb888d1f6dc4c9ae3d

Source dataset

uspto-grants-1989_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04880926