Methyl iodide → 2-Hydroxyquinoline

Temperature

-78 °C

A 10-mL RBF was charged with 6-(benzylthio)-1-((1R,2R)-2-hydroxycyclohexyl)quinolin-2(1H)-one (150 mg, 0.410 mmol) and purged with nitrogen for 10 min. TI-IF (2.1 mL) was introduced and the resultant solution cooled to −78° C. A solution of potassium bis(trimethylsilyl)amide in tetrahydrofuran (1.0M, 451 μl, 0.451 mmol) was added dropwise to the stirred reaction mixture over 2 min via syringe to produce a dark purple solution. After 15 min, iodomethane (28.0 μl, 0.451 mmol) was added dropwise via syringe and the resultant reaction mixture was allowed to warm to 0° C. After 15 min, a solution of saturated aqueous ammonium chloride was added and the reaction mixture was allowed to warm to ambient temperature and diluted with EtOAc (10 mL). The layers were separated, and the aqueous layer was further extracted with. EtOAc (3×10 mL). The combined organic layers were then washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (25-g Biotage column, eluent: gradient, 0 to 20% EtOAc in heptane) to afford (±)-6-(benzylthio)-141R,2R)-2-methoxycyclohexyl)quinolin-2(1H)-one (119 mg, 0.314 mmol, 76% yield) as a yellow solid. m/z (ESI) 380.2 (M+H)+.

1. custompurged with nitrogen for 10 min
2. additionTI-IF (2.1 mL) was introduced
3. customto produce a dark purple solution
4. customthe resultant reaction mixture
5. temperatureto warm to 0° C
6. waitAfter 15 min
7. temperatureto warm to ambient temperature
8. customThe layers were separated
9. extractionthe aqueous layer was further extracted with
10. washThe combined organic layers were then washed with brine (20 mL)
11. dry with materialdried over anhydrous magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customThe residue was purified by flash column chromatography (25-g Biotage column, eluent: gradient, 0 to 20% EtOAc in heptane)

ORD record

ord-bdcd6cc7cefe426b9915fbd707d1e0ae

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09212182B2