Iodine → 1-Chloro-7-iodoisoquinoline

Temperature

-78 °C

Into a 50 mL round-bottom flask, was placed 7-bromo-1-chloroisoquinoline (as prepared in the previous step, 520 mg, 2.15 mmol, 1.00 equiv) and tetrahydrofuran (10 mL). This was followed by the addition of n-BuLi (0.85 mL, 1.25 equiv) dropwise with stirring at −78° C. in 2 min. The resulting solution was allowed to react, with stirring, for an additional 40 min at −80° C. To this was added a solution of I2 (541 mg, 2.14 mmol, 1.25 equiv) in tetrahydrofuran (3 mL) dropwise with stirring at −78° C. in 1 min. The reaction mixture was allowed to react, with stirring, overnight at 25° C. The reaction was then quenched by the addition of 1 mL of water. The residue was diluted with 40 mL of DCM, washed with 3×15 mL of water, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by chromatography over a silica gel column with ethyl acetate/hexane (1:50). The title compound was obtained as a yellow solid.

1. customInto a 50 mL round-bottom flask, was placed
2. customto react
3. stirringwith stirring, for an additional 40 min at −80° C
4. stirringwith stirring at −78° C. in 1 min
5. customto react
6. stirringwith stirring, overnight at 25° C
7. customThe reaction was then quenched by the addition of 1 mL of water
8. additionThe residue was diluted with 40 mL of DCM
9. washwashed with 3×15 mL of water
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated under vacuum
12. customThe residue was purified by chromatography over a silica gel column with ethyl acetate/hexane (1:50)

ORD record

ord-b858b2b9deb44bf2be9de64920430cbb

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08518969B2