2-Bromo-6-iodo-3-methoxypyridine → 6-Bromo-5-methoxy-2-pyridinecarbonitrile

Temperature

-78 °C

To a solution of 2-bromo-6-iodo-3-methoxypryidine (3-1 or 5-3, 2.1 g, 6.69 mmol, 1.0 equiv) in dichloromethane (17 mL) was added isopropylmagnesium chloride (2.0 M, 4.35 mL, 8.70 mmol, 1.3 equiv) slowly at 0° C. and the reaction mixture was stirred for 45 minutes. The reaction mixture was then cooled to −78° C. and a solution of toluenesulfonyl cyanide (1.8 g, 10.03 mmol, 1.5 equiv) in dichloromethane (5 mL) was added slowly. The reaction mixture was allowed to warm to ambient temperature over 4 hours. To quench, 2 N HCl was added until neutral pH was obtained. The reaction mixture was partitioned between water and dichloromethane and the aqueous phase was extracted with dichloromethane (3×50 mL). The combined organic layer was dried over MgSO4, concentrated and the residue was purified by normal phase column chromatography (10-50% EtOAc in hexanes) to afford the product (3-2) as a tan solid. ESI+MS [M+H]+C7H6BrN2O: 212.9 found, 213.0 required.

1. temperatureto warm to ambient temperature over 4 hours
2. customTo quench
3. addition2 N HCl was added until neutral pH
4. customwas obtained
5. customThe reaction mixture was partitioned between water and dichloromethane
6. extractionthe aqueous phase was extracted with dichloromethane (3×50 mL)
7. dry with materialThe combined organic layer was dried over MgSO4
8. concentrationconcentrated
9. customthe residue was purified by normal phase column chromatography (10-50% EtOAc in hexanes)

ORD record

ord-74cf2df7b2b945149572958e61b49257

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08349872B2