Iodine → 7-Iodoquinoline

Temperature

60 °C

Quinolin-7-ylboronic acid. A mixture of 7-aminoquinoline (4.02 g, 27.9 mmol), CsI (Aldrich, 7.32 g, 28.2 mmol), iodine (Aldrich, 5.71 g, 22.5 mmol), CuI (Aldrich, 2.67 g, 14.0 mmol) and isoamyl nitrite (Aldrich, 22 mL, 19.18 g, 163.7 mmol) in 200 mL DME was heated to 60° C. After 2 h the reaction was cooled to room temperature and filtered. The filtrate was diluted with 300 mL toluene and washed consecutively with 25% NH4OH (2×100 mL), 5% Na2S2O3 (2×100 mL) and 5% NaCl (2×100 mL). The organic solution was dried over Na2SO4, evaporated onto SiO2 and purified by flash column chromatography eluting with EtOAc/Hex (0-25%) to give 7-iodoquinoline. MS (ESI, pos ion.) m/z: 256 (M+1). To a cooled (−78° C.) solution of the above 7-iodoquinoline (2.66 g, 10.4 mmol) in 20 mL THF was added 2.5M n-BuLi (5.0 mL, 12.5 mmol) drop-wise over 20 min. After an additional 20 min, B(OMe)3 (Aldrich, 3.0 mL, 26.9 mmol) was added dropwise and the reaction was warmed to room temperature. After 4 h the reaction was cooled to −78° C. and 2.5M n-BuLi (5.0 mL, 12.5 mmol) was added and the mixture allowed to warm to room temperature. After 2 h 2.5M HCl (40 mL) was added and the mixture washed with Et2O. The aqueous layer was neutralized with solid NaHCO3, extracted with 10% i-PrOH/EtOAc and the solvent removed in vacuo to give a rust colored amorphous solid. MS (ESI, pos ion). m/z: 174 (M+1).

1. temperatureAfter 2 h the reaction was cooled to room temperature
2. filtrationfiltered
3. additionThe filtrate was diluted with 300 mL toluene
4. washwashed consecutively with 25% NH4OH (2×100 mL), 5% Na2S2O3 (2×100 mL) and 5% NaCl (2×100 mL)
5. dry with materialThe organic solution was dried over Na2SO4
6. customevaporated onto SiO2
7. custompurified by flash column chromatography
8. washeluting with EtOAc/Hex (0-25%)

ORD record

ord-72523e8b35e847e4ab3b6d2d4006a195

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07314933B2