Methyl iodide → 3-Bromo-2,6-difluorotoluene

Diisopropylamine (11.9 ml, 85 mmol) is dissolved in 50 ml of anhydrous THF and cooled in a dry ice/acetone bath. n-Butyllithium (34 ml of a 2.5 M solution in hexanes, 85 mmol) is added dropwise. After 15 minutes, a solution of 1-bromo-2,4-difluorobenzene (16 g, 83 mmol) in 8 ml of THF is added at a rate to keep the temperature below −65° C. The reaction is stirred for 2.5 hours then a solution of iodomethane (10.3 ml, 166 mmol) in 8 ml of THF is added to the reaction. The ice bath is removed and the reaction is allowed to warm to room temperature. After 2 hours the reaction is quenched with water and 1N HCl. The aqueous layer is extracted twice with ether. The combined organics are washed with brine and dried over Na2SO4. Removal of the solvent affords the desired product.

1. temperaturecooled in a dry ice/acetone bath
2. customthe temperature below −65° C
3. customThe ice bath is removed
4. customAfter 2 hours the reaction is quenched with water and 1N HCl
5. extractionThe aqueous layer is extracted twice with ether
6. washThe combined organics are washed with brine
7. dry with materialdried over Na2SO4
8. customRemoval of the solvent

ORD record

ord-7f713a8c26de4622b439878e1b43ad99

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06329391B1