Methanesulfonic Acid → 6-bromo-4,4-dimethyl-3,4-dihydroisoquinolin-1(2H)-one

Temperature

0 °C

5-bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-one (1.6 g, 6.7 mmol) was dissolved in DCM (12 mL) and cooled to 0° C. Then MeSO3H (1.83 ml, 28.1 mmol) was added, followed by the portion-wise addition of NaN3 (653 mg, 10.1 mmol) over ˜10 min, while maintaining the internal reaction temperature below 5° C. The reaction was allowed to warm to room temperature and was stirred 3 h under nitrogen. At completion, the reaction was cooled to 0° C. and quenched with 8 M aq. NaOH. After stirring 30 minutes at room temperature, the quenched reaction was partitioned between DCM (50 mL) and water (50 mL). The layers were separated and the aqueous layer was extracted with DCM (2×30 mL). The combined organics were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated. 6-bromo-4,4-dimethyl-3,4-dihydroisoquinolin-1(2H)-one (711 mg, 40% yield) was isolated as a white solid after purification by flash chromatography over silica gel (eluting in 50-100% EtOAc/hexane). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.02 (br. s., 1H), 7.77 (d, J=8.0 Hz, 1H), 7.46-7.64 (m, 2H), 3.16 (d, J=3.0 Hz, 2H), 1.27 (s, 6H); MS (EI) m/z=255.1 [M+1]+.

1. temperaturewhile maintaining the internal reaction temperature below 5° C
2. temperatureto warm to room temperature
3. temperatureAt completion, the reaction was cooled to 0° C.
4. customquenched with 8 M aq. NaOH
5. stirringAfter stirring 30 minutes at room temperature
6. customthe quenched reaction
7. customwas partitioned between DCM (50 mL) and water (50 mL)
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with DCM (2×30 mL)
10. washThe combined organics were washed with brine (50 mL)
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated

ORD record

ord-7074ca035c564990acba1b9b55bc15ab

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08440652B2