tert-Butoxy bis(dimethylamino)methane → 6-Bromoisoquinolin-1(2H)-one

Temperature

140 °C

A solution of 4-bromo-2-methylbenzonitrile (26 g) dissolved in 1-tert-butoxy-N,N,N′,N′-tetramethylmethanediamine (47.9 mL) was stirred at 140° C. for 2 h (flask open to evaporate t-butanol). The reaction mixture was cooled to room temperature, diluted with water (600 mL), and extracted with ethyl acetate (500 mL). The aqueous was further extracted with ethyl acetate (250 mL), the combined organics were washed with water (500 mL), brine (150 mL), dried (MgSO4) filtered and evaporated. The residual oil was dissolved in ethanol (250 mL) at 80° C. and treated with 37% hydrochloric acid (250 mL) at such a rate as to maintain a solution. The reaction mixture was stirred at 110° C. for 3 h, cooled to room temperature, diluted with water (600 mL) and the resulting suspension stirred for 2 h and filtered. The filtered solid was slurried in diethyl ether (400 mL) for 2 h, filtered and dried to give the subtitle compound (26.4 g) as a solid.

1. custom(flask open to evaporate t-butanol)
2. temperatureThe reaction mixture was cooled to room temperature
3. additiondiluted with water (600 mL)
4. extractionextracted with ethyl acetate (500 mL)
5. extractionThe aqueous was further extracted with ethyl acetate (250 mL)
6. washthe combined organics were washed with water (500 mL), brine (150 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customevaporated
10. dissolutionThe residual oil was dissolved in ethanol (250 mL) at 80° C.
11. additiontreated with 37% hydrochloric acid (250 mL) at such a rate as
12. temperatureto maintain a solution
13. stirringThe reaction mixture was stirred at 110° C. for 3 h
14. temperaturecooled to room temperature
15. additiondiluted with water (600 mL)
16. stirringthe resulting suspension stirred for 2 h
17. filtrationfiltered
18. waitThe filtered solid was slurried in diethyl ether (400 mL) for 2 h
19. filtrationfiltered
20. customdried

ORD record

ord-b5bbf5e503e64e2095119e2c75cb78a3

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08012980B2