2-Chloro-5,6,7,8-tetrahydroquinolin-5-one → 2-Chloro-5-methyl-5,6,7,8-tetrahydroquinolin-5-ol

To a solution of 2-chloro-7,8-dihydroquinolin-5(6H)-one (500 mg, 2.75 mmol) in tetrahydrofuran (20 mL) at 0° C. was added methylmagnesium chloride (3.0 M in tetrahydrofuran, 0.92 ml, 2.8 mmol) over 2 minutes dropwise. Additional methylmagnesium chloride (3.0 M in tetrahydrofuran) were added at the following time intervals after the initial addition: 40 minutes (0.46 ml, 1.4 mmol); 60 minutes (0.46 ml, 1.4 mmol); and 120 minutes (0.92 ml, 2.8 mmol). At 1 hour after the final addition, the reaction mixture was quenched with saturated aqueous ammonium chloride solution (10 mL), and diluted with ethyl acetate (30 mL). The organic layer was separated and washed sequentially with saturated aqueous sodium bicarbonate solution and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (10-50% ethyl acetate/hexanes, linear gradient) to give 2-chloro-5-methyl-5,6,7,8-tetrahydroquinolin-5-ol. MS ESI calc'd. for C10H13ClNO [M+H]+ 198. found 198.

1. additionaddition
2. custom40 minutes (0.46 ml, 1.4 mmol)
3. custom60 minutes (0.46 ml, 1.4 mmol)
4. custom120 minutes (0.92 ml, 2.8 mmol)
5. additionAt 1 hour after the final addition
6. customthe reaction mixture was quenched with saturated aqueous ammonium chloride solution (10 mL)
7. additiondiluted with ethyl acetate (30 mL)
8. customThe organic layer was separated
9. washwashed sequentially with saturated aqueous sodium bicarbonate solution and brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe residue was purified by chromatography on silica gel (10-50% ethyl acetate/hexanes, linear gradient)

ORD record

ord-03b53ebc522a496f99e3974b2a2937d6

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216173B2