Sodium Iodide → 6-Bromo-2-(3-hydroxy-2,2-dimethylpropyl)isoquinolin-1(2H)-one

Temperature

100 °C

A solution of 6-bromoisoquinolin-1(2H)-one (Example 1b, 2.5 g) dissolved in NMP (20 mL) was treated with cesium carbonate (7.27 g) and 3-bromo-2,2-dimethylpropan-1-ol (2.75 mL) under nitrogen. The resulting mixture was stirred at 100° C. for 8 h. Further cesium carbonate (1 eq), 3-bromo-2,2-dimethylpropan-1-ol (1 eq) and water (5 mL) were added and the resulting mixture was stirred at 130° C. for 10 h. The incomplete reaction was diluted with water and extracted with ethyl acetate. The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was dissolved in NMP (20 mL) was treated with cesium carbonate (7.27 g) and 3-bromo-2,2-dimethylpropan-1-ol (2.75 mL) and sodium iodide (0.167 g) under nitrogen and heated at 130° C. for 10 h. The reaction mixture was diluted with water (250 mL), and extracted with ethyl acetate (300 mL). The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by (SiO2 chromatography, elution 60% diethyl ether in isohexane) to afford the subtitle compound (0.93 g) as a solid.

1. stirringthe resulting mixture was stirred at 130° C. for 10 h
2. customThe incomplete reaction
3. extractionextracted with ethyl acetate
4. dry with materialThe organic was dried (MgSO4)
5. filtrationfiltered
6. customevaporated
7. customto afford crude product
8. temperatureheated at 130° C. for 10 h
9. extractionextracted with ethyl acetate (300 mL)
10. dry with materialThe organic was dried (MgSO4)
11. filtrationfiltered
12. customevaporated
13. customto afford crude product
14. customThe crude product was purified by (SiO2 chromatography, elution 60% diethyl ether in isohexane)

ORD record

ord-7b6cf8667dce4a53ad8487fcc612e415

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08012980B2