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 (5-1, 2.1 g, 6.69 mmol, 1.0 equiv) in dichloromethane (17 mL) was added isopropylmagnesium chloride (2.00M, 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, 2N 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 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. addition2N 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-e5b1f2468bfb42aba4991ea0d7f56cfd

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399494B2