5-Fluoro-2-nitrophenol → 2-Amino-5-fluorophenol

To a solution of 5-fluoro-2-nitrophenol (9.50 g) in methanol (10 ml), 5% palladium on activated carbon (1.90 g) was added and stirred overnight under a hydrogen atmosphere at room temperature. The catalyst was filtered off and the solvent was distilled off under reduced pressure. The resulting residue was converted into a powder form by addition of chloroform, and then collected by filtration to give 2-amino-5-fluorophenol (6.81 g) as a brown powder. To a solution of 2-amino-5-fluorophenol thus obtained (3.00 g) in N,N-dimethylformamide (20 ml), potassium carbonate (16.31 g) and 1,2-dibromoethane (3.05 ml) were added and stirred at 125° C. for 10 hours. The reaction mixture was allowed to stand overnight at room temperature, to which additional 1,2-dibromoethane (1.52 ml) was then added and stirred at 125° C. for 7 hours. After cooling at room temperature, the reaction mixture was diluted with water under ice cooling and extracted with ethyl acetate. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate and then filtered to remove the desiccant, followed by distilling off the solvent under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=9:1 to 7:3) to give the titled compound, i.e., 7-fluoro-3,4-dihydro-2H-1,4-benzoxazine (1.15 g) as a red-brown oil.

1. filtrationThe catalyst was filtered off
2. distillationthe solvent was distilled off under reduced pressure
3. additionThe resulting residue was converted into a powder form by addition of chloroform
4. filtrationcollected by filtration

ORD record

ord-b2c62f4f67ef47d88d4ecb3a0e8c9968

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08222417B2