Hydrochloric Acid → 6-Bromo-1-methyl-1,2,3,4-tetrahydroquinolin-2-one

Temperature

0 °C

To a solution of 6-bromo-3,4-dihydroquinolin-2(1H)-one (5 g, 22.1 mmol) in DMF (100 mL) cooled to 0° C. was added potassium tert-butoxide (4.96 g, 44.2 mmol) portionwise and the reaction mixture was stirred at 0° C. for 15 min. Then, methyl iodide (4.08 g, 28.8 mmol) was added and the reaction mixture allowed to warm up to room temperature and stirring was continued over night. More MeI (1.25 g, 8.86 mmol) was added and the reaction mixture was heated to 40° C. until completion of the reaction. The mixture was diluted with EtOAc, poured into 100 mL of 1M HCl and the aqueous phase was extracted with EtOAc (2×200 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 30% EtOAc-heptane gradient to give the title compound (4.23 g, 80%) as an off white solid. MS: 240.0, 242.1 (M+H+).

1. temperatureto warm up to room temperature
2. stirringstirring
3. waitwas continued over night
4. temperaturethe reaction mixture was heated to 40° C. until completion of the reaction
5. extractionthe aqueous phase was extracted with EtOAc (2×200 mL)
6. washCombined organics were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customevaporated to dryness
10. customThe residue was purified by silica gel flash chromatography
11. washeluting with a 0 to 30% EtOAc-heptane gradient

ORD record

ord-210de72cd4b042948351689e2034df96

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260408B2