Sodium hydride → 7-bromo-2-(2,2,2-trifluoroethyl)isoquinolin-1(2H)-one

To a stirred solution of 7-bromoisoquinolin-1(2H)-one (5 g, 22.3 mmol) and iodotrifluoroethane (4.9 g, 23.4 mmol) in dimethylacetimide cooled to 5° C. was added sodium hydride 60% wt (0.89 g 22.3 mmol) portion wise over 5 minutes. After complete addition reaction mixture allowed to warm up to room temperature over 2 hours and then heated at 50° C. for 24 hours. Reaction mixture was evaporated to leave a residue, which was diluted with ethyl acetate (200 ml) and water (200 ml). The aqueous layer was further extracted with ethyl acetate (2×50 ml) and organic layers were combined and washed with saturated aqueous bicarbonate (200 ml), brine (200 ml) and dried over Magnesium sulfate powder, filtered and concentrated under reduced pressure to leave a residue and purified using column chromatography eluting with 50% ethyl acetate/petrol ether to give a yellow solid which was still impure by LCMS (1.53 g, 22% yield)

1. additionAfter complete addition reaction mixture
2. temperatureheated at 50° C. for 24 hours
3. customReaction mixture
4. customwas evaporated
5. customto leave a residue, which
6. extractionThe aqueous layer was further extracted with ethyl acetate (2×50 ml) and organic layers
7. washwashed with saturated aqueous bicarbonate (200 ml), brine (200 ml)
8. dry with materialdried over Magnesium sulfate powder
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto leave a residue
12. custompurified
13. washeluting with 50% ethyl acetate/petrol ether
14. customto give a yellow solid which

ORD record

ord-a3470d40e4d04680817a3406193a5ebc

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07767672B2