反应详情

温度

-2.5 °C

To THF (6 L) at −78° C. under N2 atmosphere was added BF3-etherate (50% assay, 708 mL, 2.81 mol) followed by slow addition of a solution of 7-bromobenzothiazole-2,5-diamine (275 g, 1.02 mol) in THF (500 mL) over 20 min. Tert-butyl nitrite (548 L, 4.61 mol) was then added to the solution at −78° C. The reaction mixture was stirred at the same temperature for 40 min then warmed to −5-0° C. Et2O was added (at −5-0° C.) and stirring continued at the same temperature for 20 min. The precipitated solid was filtered then taken in acetone at 0° C. followed by sequential addition of potassium iodide (510 g, 3.07 mol) and iodine (519 g, 2.04 mol) and stirred at 0° C. for 30 min. After the completion of reaction the mixture was quenched with a saturated solution of sodium metabisulfite then extracted with EtOAc (3×5 L). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure at 45° C. The residue thus obtained was purified over basic alumina (30-35% EtOAc-hexane) to obtain the desired product (235 g, 65%) as a light brown solid. 1H NMR (DMSO-d6): δ 7.50 (d, J=1.20 Hz, 1H), 7.63 (d, J=1.20 Hz, 1H) and 7.91 (br s, 2H). LCMS: 354.90 [M+H]+.

1. stirringstirring
2. waitcontinued at the same temperature for 20 min
3. filtrationThe precipitated solid was filtered
4. customthen taken in acetone at 0° C.
5. stirringstirred at 0° C. for 30 min
6. customAfter the completion of reaction the mixture
7. customwas quenched with a saturated solution of sodium metabisulfite
8. extractionthen extracted with EtOAc (3×5 L)
9. dry with materialThe combined organics were dried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure at 45° C
12. customThe residue thus obtained
13. customwas purified over basic alumina (30-35% EtOAc-hexane)