Iodine → 7-Bromo-5-iodobenzothiazol-2-amine

Temperature

-2.5 °C

To THF (6 L) at −78° C. under N2 was added BF3-etherate (50% assay, 708 mL, 2.81 mol) followed by a slow addition of a solution of iv (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. and the mixture was stirred at the same temperature for 40 min and then warmed to −5-0° C. Et2O was added (at −5-0° C.) and the mixture stirred for 20 min. The solid was filtered and taken in acetone at 0° C. followed by sequential addition of KI (510 g, 3.07 mol) and iodine (519 g, 2.04 mol) and the mixture stirred at 0° C. for 30 min. The reaction was quenched with saturated solution of sodium metabisulfite and extracted with EtOAc (3×5 L). The combined organics were dried (Na2SO4), filtered and concentrated in vacuo at 45° C. The residue was purified over basic alumina (30-35% EtOAc-hexane) to obtain v (235 g, 65%). 1H NMR (DMSO-d6, 400 MHz): δ 7.50 (d, J=1.20 Hz, 1H), 7.63 (d, J=1.20 Hz, 1H) and 7.91 (br s, 2H). MS: 354.90 [M+H]+.

1. stirringthe mixture stirred for 20 min
2. filtrationThe solid was filtered
3. customtaken in acetone at 0° C.
4. stirringthe mixture stirred at 0° C. for 30 min
5. customThe reaction was quenched with saturated solution of sodium metabisulfite
6. extractionextracted with EtOAc (3×5 L)
7. dry with materialThe combined organics were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo at 45° C
10. customThe residue was purified over basic alumina (30-35% EtOAc-hexane)
11. customto obtain v (235 g, 65%)

ORD record

ord-2b2a130aca924a4ca84e991977bce392

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08906902B2