Methyl iodide → 5-fluoro-2-methyl-8-nitro-3,4-dihydro-2H-isoquinolin-1-one

To a solution of 3-fluoro-2-(2-methoxycarbonylamino-ethyl)-6-nitro-benzoic acid methyl ester (20.4 g, 68 mmol) in THF (200 mL), sodium hydride (5.44 g, 136 mmol) was added at 0° C. and the mixture was stirred at rt for 2.0 hrs. To the reaction mixture was added methyl iodide (12.7 mL, 204 mmol) at 0° C. and the mixture was stirred at rt for 1.5 hours. To the mixture was added saturated ammonium chloride solution at 0° C., and the mixture was extracted three times with ethyl acetate. The organic layer was washed twice with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (dichloromethane/ethyl acetate/hexane: from 99/1/50 to 99/2/50) to give 5-fluoro-2-methyl-8-nitro-3,4-dihydro-2H-isoquinolin-1-one (10.9 g) as yellow solid in 71% yield.

1. stirringthe mixture was stirred at rt for 1.5 hours
2. extractionthe mixture was extracted three times with ethyl acetate
3. washThe organic layer was washed twice with water and brine
4. dry with materialdried over magnesium sulfate
5. customevaporated in vacuo
6. customThe residue was purified by silica gel column chromatography (dichloromethane/ethyl acetate/hexane: from 99/1/50 to 99/2/50)

ORD record

ord-5306b23efed9473086e8deda07b96f5e

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07910585B2